CTGF基因干扰对转化生长因子β_2诱导的人晶状体上皮细胞间质转分化的调控研究
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摘要
研究目的:后发障是现代白内障术后最常见的并发症,后发障的发病机制至今尚未完全明确。上皮间质转分化是后发障发生过程中主的要病理改变,转化生长因子β(TGF-β)作为间质转分化最有力的诱导因子,在后发障发病过程中发挥重要作用。阻断TGF-β诱导的间质转分化的生物学过程为后发障的防治提供了新的思路。结缔组织生长因子(CTGF)是一种在纤维化过程中起重要作用的间质细胞生长因子,近年来CTGF在TGF-β诱导的一系列生物学过程,特别是间质转分化过程中的作用受到重视。本课题旨在总结以往研究TGF-β与后发障相关研究的基础上,采用siRNA干扰这一高效、特异的基因沉默手段抑制体外培养的人晶状体上皮细胞CTGF的表达,观察基因干扰对TGF-β_2诱导的上皮间质转分化的影响,分析TGF-β_2和CTGF在晶状体上皮细胞间质转分化过程中的作用及信号转导机制,进一步明确后发障的发病机制,为基因治疗后发障提供靶标。
研究方法:采用体外培养的人晶状体上皮细胞株HLE B-3,用不同浓度的TGF-β_2处理细胞,应用免疫印迹法及RT-PCR观察细胞CTGF表达及间质转分化相关蛋白connexin43、a-SMA表达的影响。建立后发障离体研究模型,采用脂质体介导的siRNA干扰技术转染HLE B-3细胞,特异性沉默CTGF的表达。应用免疫印迹、免疫荧光等方法观察CTGF基因干扰对TGF-β_2诱导的晶状体上皮细胞间质转分化及粘附功能的影响。
研究结果:TGF-β_2能够诱导体外培养人晶状体上皮细胞表达CTGF蛋白,CTGF在晶状体上皮细胞内的表达主要位于细胞浆。外源性TGF-β_2及CTGF均能诱导人晶状体上皮细胞发生间质转分化。siRNA干扰能够成功的从基因和蛋白水平抑制TGF-β_2诱导的人晶状体上皮细胞CTGF的表达,并且能够抑制TGF-β_2诱导的人晶状上皮细胞间质转分化和粘附作用及相关蛋白的表达。
研究结论:CTGF作为TGF-β_2的下游分子,在TGF-β_2诱导的晶状体上皮细胞的间质转分化过程中发挥关键作用。基因干扰CTGF的表达能够抑制TGF-β_2诱导的晶状体上皮细胞间质转分化,为后发障的防治提供理论依据。
Objective:Posterior capsular opacification(PCO) is the main complication of modern cataract surgery and cause of poor vision post-operation.Residual lens epithelial cells (LECs) undergo epithelial mesenchymal transition(EMT) in the progress of PCO. Previous work has revealed that transforming growth factor beta(TGF-β)play an important role in PCO.Though it is extensively studied,the mechanism of TGF-βon lens is complex and not completely understood yet.Connective tissue growth factor (CTGF) is a matricellular protein that has been found to participate in EMT.So it is critical to understand the mechanism of CTGF,a potent growth factor in ocular media, in process of EMT in LECs.On the basis of previous studies,we established a research model for PCO in vitro.We also took the siRNA technique to selectively silence the expression of CTGF in LECs to investigate the role of CTGF in TGF-β_2 induced EMT in human lens epithelial cells.
Methods:HLE B-3 cells were treated with different concentrations of TGF-β_2 to investigate effect of TGF-β_2 on expression of CTGF,connexin43 and a-SMA with western blot and RT-PCR.siRNA technique was operated to selectively silence the expression of CTGF gene.Then we analyzed the effect of siRNA interfere on TGF-β_2 induced EMT and adhesion of LECs with western blot and immunofluorescence.
Results:HLE B-3 cells underwent morphological alteration and EMT under TGF-β_2 stimulation concomitant with dramatic up-regulation of CTGF mRNA and protein levels.The expression of Connexin43 was decreased after treatment of TGF-β_2,while the expression of a-SMA was increased.CTGF silencing by CTGF siRNA approaches showed that TGF-β_2-induced EMT and adhesion were CTGF dependent.
Conclusion:CTGF is an essential downstream mediator of TGF-β_2-induced EMT in lens epithelial ceils.Selectively silence the expression of CTGF could be a potent therapeutic target of PCO.
研究方法:采用体外培养的人晶状体上皮细胞株HLE B-3,用不同浓度的TGF-β_2处理细胞,应用免疫印迹法及RT-PCR观察细胞CTGF表达及间质转分化相关蛋白connexin43、a-SMA表达的影响。建立后发障离体研究模型,采用脂质体介导的siRNA干扰技术转染HLE B-3细胞,特异性沉默CTGF的表达。应用免疫印迹、免疫荧光等方法观察CTGF基因干扰对TGF-β_2诱导的晶状体上皮细胞间质转分化及粘附功能的影响。
研究结果:TGF-β_2能够诱导体外培养人晶状体上皮细胞表达CTGF蛋白,CTGF在晶状体上皮细胞内的表达主要位于细胞浆。外源性TGF-β_2及CTGF均能诱导人晶状体上皮细胞发生间质转分化。siRNA干扰能够成功的从基因和蛋白水平抑制TGF-β_2诱导的人晶状体上皮细胞CTGF的表达,并且能够抑制TGF-β_2诱导的人晶状上皮细胞间质转分化和粘附作用及相关蛋白的表达。
研究结论:CTGF作为TGF-β_2的下游分子,在TGF-β_2诱导的晶状体上皮细胞的间质转分化过程中发挥关键作用。基因干扰CTGF的表达能够抑制TGF-β_2诱导的晶状体上皮细胞间质转分化,为后发障的防治提供理论依据。
Objective:Posterior capsular opacification(PCO) is the main complication of modern cataract surgery and cause of poor vision post-operation.Residual lens epithelial cells (LECs) undergo epithelial mesenchymal transition(EMT) in the progress of PCO. Previous work has revealed that transforming growth factor beta(TGF-β)play an important role in PCO.Though it is extensively studied,the mechanism of TGF-βon lens is complex and not completely understood yet.Connective tissue growth factor (CTGF) is a matricellular protein that has been found to participate in EMT.So it is critical to understand the mechanism of CTGF,a potent growth factor in ocular media, in process of EMT in LECs.On the basis of previous studies,we established a research model for PCO in vitro.We also took the siRNA technique to selectively silence the expression of CTGF in LECs to investigate the role of CTGF in TGF-β_2 induced EMT in human lens epithelial cells.
Methods:HLE B-3 cells were treated with different concentrations of TGF-β_2 to investigate effect of TGF-β_2 on expression of CTGF,connexin43 and a-SMA with western blot and RT-PCR.siRNA technique was operated to selectively silence the expression of CTGF gene.Then we analyzed the effect of siRNA interfere on TGF-β_2 induced EMT and adhesion of LECs with western blot and immunofluorescence.
Results:HLE B-3 cells underwent morphological alteration and EMT under TGF-β_2 stimulation concomitant with dramatic up-regulation of CTGF mRNA and protein levels.The expression of Connexin43 was decreased after treatment of TGF-β_2,while the expression of a-SMA was increased.CTGF silencing by CTGF siRNA approaches showed that TGF-β_2-induced EMT and adhesion were CTGF dependent.
Conclusion:CTGF is an essential downstream mediator of TGF-β_2-induced EMT in lens epithelial ceils.Selectively silence the expression of CTGF could be a potent therapeutic target of PCO.
引文
1. Busbee BG,Brown GC,Brown MM.Cost-effectiveness of ocular interventions.Curr Opin Ophthalmol 2003;14(3):132-8.
2. Wormstone IM.Posterior capsule opacification:a cell biological perspective.Exp Eye Res 2002;74(3):337-47.
3. Taylor HR.Cataract:how much surgery do we have to do? Br J Ophthalmol 2000;84(1):1-2.
4. Dewey S.Posterior capsule opacification.Curr Opin Ophthalmol 2006;17(1):45-53.
5. Bertelmann E,Kojetinsky C.Posterior capsule opacification and anterior capsule opacification.Curr Opin Ophthalmol 2001;12(1):35-40.
6. Pandey SK,Apple DJ,Werner L,Maloof AJ,Milverton EJ.Posterior capsule opacification:a review of the aetiopathogenesis,experimental and clinical studies and factors for prevention.Indian J Ophthalmol 2004;52(2):99-112.
7. Aslam TM,Devlin H,Dhillon B.Use of Nd:YAG laser capsulotomy.Surv Ophthalmol 2003;48(6):594-612.
8. Bunting HJ,Laganowski H.Routine follow-up after YAG laser capsulotomy for posterior capsule opacification.Eye 2006;20(12):1449-50.
9. Billotte C,Berdeaux G.Adverse clinical consequences of neodymium:YAG laser treatment of posterior capsule opacification.J Cataract.Refract Surg 2004;30(10):2064-71.
10. Apple DJ,Solomon KD,Tetz MR,Assia EI,Holland EY,Legler UF,Tsai JC,Castaneda VE,Hoggatt JP,Kostick AM.Posterior capsule opacification.Surv Ophthalmol 1992;37(2):73-116.
11. Wormstone IM,Wang L,Liu CS.Posterior capsule opacification.Exp Eye Res 2009;88(2):257-69.
12. Gordon-Thomson C,de Iongh RU,Hales AM,Chamberlain CG,McAvoy JW.Differential cataractogenic potency of TGF-betal,-beta2,and-beta3 and their expression in the postnatal rat eye.Invest Ophthalmol Vis Sci 1998;39(8):1399-409.
13. Shirai K,Saika S,Okada Y,Oda S,Ohnishi Y.Histology and immunohistochemistry of fibrous posterior capsule opacification in an infant.J Cataract Refract Surg 2004;30(2):523-6.
14. de Iongh RU,Wederell E,Lovicu FJ,McAvoy JW.Transforming growth factor-beta-induced epithelial-mesenchymal transition in the lens:a model for cataract formation.Cells Tissues Organs 2005;179(1-2):43-55.
15. de Iongh RU,Gordon-Thomson C,Chamberlain CG,Hales AM,McAvoy JW.Tgfbeta receptor expression in lens:implications for differentiation and cataractogenesis.Exp Eye Res 2001;72(6):649-59.
16. Jampel HD,Roche N,Stark WJ,Roberts AB.Transforming growth factor-beta in human aqueous humor.Curr Eye Res 1990;9(10):963-9.
17. Dawes LJ,Eldred JA,Anderson IK,Sleeman M,Reddan JR,Duncan G,Wormstone IM.TGF beta-induced contraction is not promoted by fibronectin-fibronectin receptor interaction,or alpha SMA expression.Invest Ophthalmol Vis Sci 2008;49(2):650-61.
18. Yao K,Ye PP,Tan J,Tang XJ,Shen Tu XC.Involvement of PI3K/Akt pathway in TGF-beta2-mediated epithelial mesenchymal transition in human lens epithelial cells.Ophthalmic Res 2008;40(2):69-76.
19. Yao K,Tan J,Ye P,Wang K,Xu W,ShenTu X,Tang X.Integrin betal-mediated signaling is involved in transforming growth factor-beta2-promoted migration in human lens epithelial cells.Mol Vis 2007;13:1769-76.
20. Yao K,Tan J,Gu WZ,Ye PP,Wang KJ.Reactive oxygen species mediates the apoptosis induced by transforming growth factor beta(2)in human lens epithelial cells.Biochem Biophys Res Commun 2007;354(1):278-83.
21. Bradham DM,Igarashi A,Potter RL,Grotendorst GR.Connective tissue growth factor:a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10.J Cell Biol 1991;114(6):1285-94.
22. Williams EJ,Gaca MD,Brigstock DR,Arthur MJ,Benyon RC.Increased expression of connective tissue growth factor in fibrotic human liver and in activated hepatic stellate cells.J Hepatol 2000;32(5):754-61.
23. Murphy M,Godson C,Cannon S,Kato S,Mackenzie HS,Martin F,Brady HR.Suppression subtractive hybridization identifies high glucose levels as a stimulus for expression of connective tissue growth factor and other genes in human mesangial cells.J Biol Chem 1999;274(9):5830-4.
24. Igarashi A,Okochi H,Bradham DM,Grotendorst GR.Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair.Mol Biol Cell 1993;4(6):637-45.
25. Rachfal AW,Brigstock DR.Structural and functional properties of CCN proteins.Vitam Horm 2005;70:69-103.
26. Moussad EE,Brigstock DR.Connective tissue growth factor:what's in a name? Mol Genet Metab 2000;71(1-2):276-92.
27. Kothapalli D,Hayashi N,Grotendorst GR.Inhibition of TGF-beta-stimulated CTGF gene expression and anchorage-independent growth by cAMP identifies a CTGF-dependent restriction point in the cell cycle.FASEB J 1998;12(12):1151-61.
28. Gao R,Ball DK,Perbal B,Brigstock DR.Connective tissue growth factor induces c-fos gene activation and cell proliferation through p44/42 MAP kinase in primary rat hepatic stellate cells.J Hepatol 2004;40(3):431-8.
29. Song JJ,Aswad R,Kanaan RA,Rico MC,Owen TA,Barbe MF,Safadi FF, Popoff SN.Connective tissue growth factor(CTGF)acts as a downstream mediator of TGF-betal to induce mesenchymal cell condensation.J Cell Physiol 2007;210(2):398-410.
30. Gao R,Brigstock DR.A novel integrin alpha5betal binding domain in module 4 of connective tissue growth factor(CCN2/CTGF)promotes adhesion and migration of activated pancreatic stellate cells.Gut 2006;55(6):856-62.
31. Korner T,Kropf J,Kosche B,Kristahl H,Jaspersen D,Gressner AM.Improvement of prognostic power of the Child-Pugh classification of liver cirrhosis by hyaluronan.J Hepatol 2003;39(6):947-53.
32. Wahab NA,Mason RM.A critical look at growth factors and epithelial-to-mesenchymal transition in the adult kidney.Interrelationships between growth factors that regulate EMT in the adult kidney.Nephron Exp Nephrol 2006;104(4):e129-34.
33. Lee EH,Joo CK.Role of transforming growth factor-beta in transdifferentiation and fibrosis of lens epithelial cells.Invest Ophthalmol Vis Sci 1999;40(9):2025-32.
34. Wunderlich K,Pech M,Eberle AN,Mihatsch M,Flammer J,Meyer P.Expression of connective tissue growth factor(CTGF)mRNA in plaques of human anterior subcapsular cataracts and membranes of posterior capsule opacification.Curr Eye Res 2000;21(2):627-36.
35. Wormstone IM,Tamiya S,Eldred JA,Lazaridis K,Chantry A,Reddan JR,Anderson I,Duncan G.Characterisation of TGF-beta2 signalling and function in a human lens cell line.Exp Eye Res 2004;78(3):705-14.
36. Garrett Q,Khaw PT,Blalock TD,Schultz GS,Grotendorst GR,Daniels JT.Involvement of CTGF in TGF-betal-stimulation of myofibroblast differentiation and collagen matrix contraction in the presence of mechanical stress.Invest Ophthalmol Vis Sci 2004;45(4):1109-16.
37. Elbashir SM,Martinez J,Patkaniowska A,Lendeckel W,Tuschl T.Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate.EMBO J 2001;20(23):6877-88.
38. Zhou HJ,Tsai SY,Tsai MJ.RNAi technology and its use in studying the function of nuclear receptors and coregulators.Nucl Recept Signal 2003;1:e008.
39. Donze O,Picard D.RNA interference in mammalian cells using siRNAs synthesized with T7 RNA polymerase.Nucleic Acids Res 2002;30(10):e46.
40. Fire A,Xu S,Montgomery MK,Kostas SA,Driver SE,Mello CC.Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans.Nature 1998;391(6669):806-1
1.Bradham DM,Igarashi A,Potter RL,Grotendorst GR.Connective tissue growth factor:a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10.J Cell Biol 1991;114(6):1285-94.
2. Williams EJ,Gaca MD,Brigstock DR,Arthur MJ,Benyon RC.Increased expression of connective tissue growth factor in fibrotic human liver and in activated hepatic stellate cells.J Hepatol 2000;32(5):754-61.
3. Murphy M,Godson C,Cannon S,Kato S,Mackenzie HS,Martin F,et al.Suppression subtractive hybridization identifies high glucose levels as a stimulus for expression of connective tissue growth factor and other genes in human mesangial cells.J Biol Chem 1999;274(9):5830-4.
4. Igarashi A,Okochi H,Bradham DM,Grotendorst GR.Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair.Mol Biol Cell 1993;4(6):637-45.
5. Lee EH,Joo CK.Role of transforming growth factor-beta in transdifferentiation and fibrosis of lens epithelial cells.Invest Ophthalmol Vis Sci 1999;40(9):2025-32.
6. van Setten GB,Blalock TD,Grotendorst G,Schultz GS.Detection of connective tissue growth factor in human aqueous humor.Ophthalmic Res 2002;34(5):306-8.
7. van Setten GB,Blalock TD,Grotendorst G,Schultz GS.Detection of connective tissue growth factor(CTGF)in human tear fluid:preliminary results.Acta Ophthalmol Scand 2003;81(1):51-3.
8. Ho SL,Dogar GE,Wang J,Crean J,Wu QD,Oliver N,et al.Elevated aqueous humour tissue inhibitor of matrix metalloproteinase-1 and connective tissue growth factor in pseudoexfoliation syndrome.Br J Ophthalmol 2005;89(2):169-73.
9. Wunderlich K,Pech M,Eberle AN,Mihatsch M,Flammer J,Meyer P.Expression of connective tissue growth factor(CTGF)mRNA in plaques of human anterior subcapsular cataracts and membranes of posterior capsule opacification.Curr Eye Res 2000;21(2):627-36.
10.Wormstone IM,Tamiya S,Eldred JA,Lazaridis K,Chantry A,Reddan JR,et al.Characterisation of TGF-beta2 signalling and function in a human lens cell line.Exp Eye Res 2004;78(3):705-14.
11.Andley UP,Rhim JS,Chylack LT,Jr.,Fleming TP.Propagation and immortalization of human lens epithelial cells in culture.Invest Ophthalmol Vis Sci 1994;35(7):3094-102.
12.Yao K,Ye PP,Tan J,Tang XJ,Shen Tu XC.Involvement of PI3K/Akt pathway in TGF-beta2-mediated epithelial mesenchymal transition in human lens epithelial cells.Ophthalmic Res 2008;40(2):69-76.
13.Massague J.The transforming growth factor-beta family.Annu Rev Cell Biol 1990;6:597-641.
14.Saika S.TGFbeta pathobiology in the eye.Lab Invest 2006;86(2):106-15.
15.Yao K,Tan J,Ye P,Wang K,Xu W,ShenTu X,et al.Integrin betal-mediated signaling is involved in transforming growth factor-beta2-promoted migration in human lens epithelial cells.Mol Vis 2007;13:1769-76.
16.Yao K,Tan J,Gu WZ,Ye PP,Wang KJ.Reactive oxygen species mediates the apoptosis induced by transforming growth factor beta(2)in human lens epithelial cells.Biochem Biophys Res Commun 2007;354(1):278-83.
17.Wahab NA,Brinkman H,Mason RM.Uptake and intracellular transport of the connective tissue growth factor:a potential mode of action.Biochem J 2001;359(Pt 1):89-97.
18.Chen Y,Segarini P,Raoufi F,Bradham D,Leask A.Connective tissue growth factor is secreted through the Golgi and is degraded in the endosome.Exp Cell Res 2001; 271(1):109-17.
19.Dziadzio M,Usinger W,Leask A,Abraham D,Black CM,Denton C,et al.N-terminal connective tissue growth factor is a marker of the fibrotic phenotype in scleroderma.QJM 2005;98(7):485-92.
20.Okamura M,Yamaji S,Nagashima Y,Nishikawa M,Yoshimoto N,Kido Y,et al.Prognostic value of integrin betal-ILK-pAkt signaling pathway in non-small cell lung cancer.Hum Pathol 2007;38(7):1081-91.
21.Mori T,Kawara S,Shinozaki M,Hayashi N,Kakinuma T,Igarashi A,et al.Role and interaction of connective tissue growth factor with transforming growth factor-beta in persistent fibrosis:A mouse fibrosis model.J Cell Physiol 1999;181(1):153-9.
22.Burns WC,Twigg SM,Forbes JM,Pete J,Tikellis C,Thallas-Bonke V,et al.Connective tissue growth factor plays an important role in advanced glycation end product-induced tubular epithelial-to-mesenchymal transition:implications for diabetic renal disease.J Am Soc Nephrol 2006;17(9):2484-94.
23.Song JJ,Aswad R,Kanaan RA,Rico MC,Owen TA,Barbe MF,et al.Connective tissue growth factor(CTGF)acts as a downstream mediator of TGF-betal to induce mesenchymal cell condensation.J Cell Physiol 2007;210(2):398-410.
24.Arnott JA,Nuglozeh E,Rico MC,Arango-Hisijara I,Odgren PR,Safadi FF,et al.Connective tissue growth factor(CTGF/CCN2)is a downstream mediator for TGF-b1-induced extracellular matrix production in osteoblasts.Jounal of cellular physiology 2007;210:843-52.
25.Ihn H.Pathogenesis of fibrosis:role of TGF-beta and CTGF.Curr Opin Rheumatol 2002;14(6):681-5.
26.Grotendorst GR,Okochi H,Hayashi N.A novel transforming growth factor beta response element controls the expression of the connective tissue growth factor gene.Cell Growth Differ 1996;7(4):469-80.
27.Leask A,Holmes A,Black CM,Abraham DJ.Connective tissue growth factor gene regulation.Requirements for its induction by transforming growth factor-beta 2 in fibroblasts.J Biol Chem 2003;278(15):13008-15.
28.Holmes A,Abraham DJ,Sa S,Shiwen X,Black CM,Leask A.CTGF and SMADs,maintenance of scleroderma phenotype is independent of SMAD signaling.J Biol Chem 2001;276(14):10594-601.
29.Samarakoon R,Higgins CE,Higgins SP,Higgins PJ.Differential requirement for MEK/ERK and SMAD signaling in PAI-1 and CTGF expression in response to microtubule disruption.Cell Signal 2009;21(6):986-95.
30.Secker GA,Shortt AJ,Sampson E,Schwarz QP,Schultz GS,Daniels JT.TGFbeta stimulated re-epithelialisation is regulated by CTGF and Ras/MEK/ERK signalling.Exp Cell Res 2008;314(1):131-42.
31.Yosimichi G,Kubota S,Nishida T,Kondo S,Yanagita T,Nakao K,et al.Roles of PKC,PI3K and JNK in multiple transduction of CCN2/CTGF signals in chondrocytes.Bone 2006;38(6):853-63.
32.Chen Y,Blom IE,Sa S,Goldschmeding R,Abraham DJ,Leask A.CTGF expression in mesangial cells:involvement of SMADs,MAP kinase,and PKC.Kidney Int 2002;62(4):1149-59.
1. Apple DJ,Solomon KD,Tetz MR,Assia EI,Holland EY,Legler UF,et al.Posterior capsule opacification.Surv Ophthalmol 1992;37(2):73-116.
2. Apple DJ,Peng Q,Visessook N,Werner L,Pandey SK,Escobar-Gomez M,et al.Eradication of posterior capsule opacification:documentation of a marked decrease in Nd:YAG laser posterior capsulotomy rates noted in an analysis of 5416 pseudophakic human eyes obtained postmortem.Ophthalmology 2001;108(3):505-18.
3. Hutchinson AK,Wilson ME,Saunders RA.Outcomes and ocular growth rates after intraocular lens implantation in the first 2 years of life.J Cataract Refract Surg 1998;24(6):846-52.
4. Fagerholm P,Lundevall E,Trocme S,Wroblewski R.Human and experimental lens repair and calcification.Exp Eye Res 1986;43(6):965-72.
5. Prakash G,Jhanji V,Sharma N,Titiyal JS.Posterior capsule opacification in diabetic patients.J Cataract Refract Surg 2007;33(3):363-4.
6. Bras ID,Colitz CM,Saville WJ,Gemensky-Metzler AJ,Wilkie DA.Posterior capsular opacification in diabetic and nondiabetic canine patients following cataract surgery.Vet Ophthalmol 2006;9(5):317-27.
7. Aslam TM,Devlin H,Dhillon B.Use of Nd:YAG laser capsulotomy.Surv Ophthalmol 2003;48(6):594-612.
8. Bunting HJ,Laganowski H.Routine follow-up after YAG laser capsulotomy for posterior capsule opacification.Eye 2006;20(12):1449-50.
9. Billotte C,Berdeaux G.Adverse clinical consequences of neodymium:YAG laser treatment of posterior capsule opacification.J Cataract Refract Surg 2004;30(10):2064-71.
10.Lee JM,Dedhar S,Kalluri R,Thompson EW.The epithelial-mesenchymal transition:new insights in signaling,development,and disease.J Cell Biol 2006; 172(7):973-81.
11.Lovicu FJ,Schulz MW,Hales AM,Vincent LN,Overbeek PA,Chamberlain CG,et al.TGFbeta induces morphological and molecular changes similar to human anterior subcapsular cataract.Br J Ophthalmol 2002;86(2):220-6.
12.Marcantonio JM,Syam PP,Liu CS,Duncan G Epithelial transdifferentiation and cataract in the human lens.Exp Eye Res 2003;77(3):339-46.
13.Shirai K,Saika S,Okada Y,Oda S,Ohnishi Y.Histology and immunohistochemistry of fibrous posterior capsule opacification in an infant.J Cataract Refract Surg 2004;30(2):523-6.
14.Zavadil J,Cermak L,Soto-Nieves N,Bottinger EP.Integration of TGF-beta/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition.EMBO J 2004;23(5):1155-65.
15.Wahab NA,Weston BS,Mason RM.Modulation of the TGFbeta/Smad signaling pathway in mesangial cells by CTGF/CCN2.Exp Cell Res 2005;307(2):305-14.
16.Wahab NA,Mason RM.A critical look at growth factors and epithelial-to-mesenchymal transition in the adult kidney.Interrelationships between growth factors that regulate EMT in the adult kidney.Nephron Exp Nephrol 2006;104(4):e129-34.
17.Zeisberg M,Hanai J,Sugimoto H,Mammoto T,Charytan D,Strutz F,et al.BMP-7 counteracts TGF-betal-induced epithelial-to-mesenchymal transition and reverses chronic renal injury.Nat Med 2003;9(7):964-8.
18.Abreu JG,Ketpura NI,Reversade B,De Robertis EM.Connective-tissue growth factor(CTGF)modulates cell signalling by BMP and TGF-beta.Nat Cell Biol 2002;4(8):599-604.
19.Gore-Hyer E,Shegogue D,Markiewicz M,Lo S,Hazen-Martin D,Greene EL,et al.TGF-beta and CTGF have overlapping and distinct fibrogenic effects on human renal cells.Am J Physiol Renal Physiol 2002;283(4):F707-16.
20.Weston BS,Wahab NA,Mason RM.CTGF mediates TGF-beta-induced fibronectin matrix deposition by upregulating active alpha5betal integrin in human mesangial cells.J Am Soc Nephrol 2003;14(3):601-10.
21.Leask A.Transcriptional profiling of the scleroderma fibroblast reveals a potential role for connective tissue growth factor(CTGF)in pathological fibrosis.Keio J Med 2004;53(2):74-7.
22.Yao K,Tan J,Gu WZ,Ye PP,Wang KJ.Reactive oxygen species mediates the apoptosis induced by transforming growth factor beta(2)in human lens epithelial cells.Biochem Biophys Res Commun 2007;354(1):278-83.
23.Yao K,Tan J,Ye P,Wang K,Xu W,ShenTu X,et al.Integrin betal-mediated signaling is involved in transforming growth factor-beta2-promoted migration in human lens epithelial cells.Mol Vis 2007;13:1769-76.
24.Yao K,Ye PP,Tan J,Tang XJ,Shen Tu XC.Involvement of PI3K/AM pathway in TGF-beta2-mediated epithelial mesenchymal transition in human lens epithelial cells.Ophthalmic Res 2008;40(2):69-76.
25.Awasthi N,Wagner BJ.Suppression of human lens epithelial cell proliferation by proteasome inhibition,a potential defense against posterior capsular opacification.Invest Ophthalmol Vis Sci 2006;47(10):4482-9.
26.Donaldson PJ,Roos M,Evans C,Beyer E,Kistler J.Electrical properties of mammalian lens epithelial gap junction channels.Invest Ophthalmol Vis Sci 1994;35(9):3422-8.
27.Gupta VK,Berthoud VM,Atal N,Jarillo JA,Barrio LC,Beyer EC.Bovine connexin44,a lens gap junction protein:molecular cloning,immunologic characterization,and functional expression.Invest Ophthalmol Vis Sci 1994;35(10):3747-58.
28.Gu S,Yu XS,Yin X,Jiang JX.Stimulation of lens cell differentiation by gap junction protein connexin 45.6.Invest Ophthalmol Vis Sci 2003;44(5):2103-11.
29.Le AC,Musil LS.A novel role for FGF and extracellular signal-regulated kinase in gap junction-mediated intercellular communication in the lens.J Cell Biol 2001;154(1):197-216.
30.Lovicu FJ,Steven P,Saika S,McAvoy JW.Aberrant lens fiber differentiation in anterior subcapsular cataract formation:a process dependent on reduced levels of Pax6.Investigative ophthalmology & visual science 2004;45(6):1946-53.
31.Krutovskikh VA,Troyanovsky SM,Piccoli C,Tsuda H,Asamoto M,Yamasaki H.Differential effect of subcellular localization of communication impairing gap junction protein connexin43 on tumor cell growth in vivo.Oncogene 2000;19(4):505-13.
32.Maass K,Shibayama J,Chase SE,Willecke K,Delmar M.C-terminal truncation of connexin43 changes number,size,and localization of cardiac gap junction plaques.Circ Res 2007;101(12):1283-91.
33.Xie H,Laird DW,Chang TH,Hu VW.A mitosis-specific phosphorylation of the gap junction protein connexin43 in human vascular cells:biochemical characterization and localization.J Cell Biol 1997;137(1):203-10.
34.Fatigati V,Murphy RA.Actin and tropomyosin variants in smooth muscles.Dependence on tissue type.J Biol Chem 1984;259(23):14383-8.
35.Cobo LM,Ohsawa E,Chandler D,Arguello R,George G.Pathogenesis of capsular opacification after extracapsular cataract extraction.An animal model.Ophthalmology 1984;91(7):857-63.
36.de Iongh RU,Wederell E,Lovicu FJ,McAvoy JW.Transforming growth factor-beta-induced epithelial-mesenchymal transition in the lens:a model for cataract formation.Cells Tissues Organs 2005;179(1-2):43-55.
37.Lee EH,Joo CK.Role of transforming growth factor-beta in transdifferentiation and fibrosis of lens epithelial cells.Invest Ophthalmol Vis Sci 1999;40(9):2025-32.
38.Hannigan GE,Leung-Hagesteijn C,Fitz-Gibbon L,Coppolino MG,Radeva G,Filmus J,et al.Regulation of cell adhesion and anchorage-dependent growth by a new beta 1-integrin-linked protein kinase.Nature 1996;379(6560):91-6.
39.Weaver MS,Toida N,Sage EH.Expression of integrin-linked kinase in the murine lens is consistent with its role in epithelial-mesenchymal transition of lens epithelial cells in vitro.Mol Vis 2007;13:707-18.
40.van Setten GB,Blalock TD,Grotendorst G,Schultz GS.Detection of connective tissue growth factor in human aqueous humor.Ophthalmic Res 2002;34(5):306-8.
41.Ho SL,Dogar GF,Wang J,Crean J,Wu QD,Oliver N,et al.Elevated aqueous humour tissue inhibitor of matrix metalloproteinase-1 and connective tissue growth factor in pseudoexfoliation syndrome.Br J Ophthalmol 2005;89(2):169-73.
42.Grotendorst GR,Okochi H,Hayashi N.A novel transforming growth factor beta response element controls the expression of the connective tissue growth factor gene.Cell Growth Differ 1996;7(4):469-80.
43.Olivero DK,Furcht LT.Type IV collagen,laminin,and fibronectin promote the adhesion and migration of rabbit lens epithelial cells in vitro.Invest Ophthalmol Vis Sci 1993;34(10):2825-34.
44.Negash S,Wang HS,Gao C,Ledee D,Zelenka P.Cdk5 regulates cell-matrix and cell-cell adhesion in lens epithelial cells.J Cell Sci 2002;115(Pt 10):2109-17.
45.Weaver MS,Sage EH,Yan Q.Absence of SPARC in lens epithelial cells results in altered adhesion and extracellular matrix production in vitro.J Cell Biochem 2006;97(2):423-32.
46.Schlaepfer DD,Hanks SK,Hunter T,van der Geer P.Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase.Nature 1994;372(6508):786-91.
47.Richardson A,Parsons JT.Signal transduction through integrins:a central role for focal adhesion kinase.Bioessays 1995;17(3):229-36.
48.Schlaepfer DD,Hauck CR,Sieg DJ.Signaling through focal adhesion kinase.Prog Biophys Mol Biol 1999;71(3-4):435-78.
1. Bradham DM,Igarashi A,Potter RL,Grotendorst GR.Connective tissue growth factor:a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10.J Cell Biol 1991;114(6):1285-94.
2. Leask A,Abraham DJ.All in the CCN family:essential matricellular signaling modulators emerge from the bunker.J Cell Sci 2006;119(Pt 23):4803-10.
3. Rachfal AW,Brigstock DR.Structural and functional properties of CCN proteins.Vitam Horm 2005;70:69-103.
4. Bork P.The modular architecture of a new family of growth regulators related to connective tissue growth factor.FEBS Lett 1993;327(2):125-30.
5. Williams EJ,Gaca MD,Brigstock DR,Arthur MJ,Benyon RC.Increased expression of connective tissue growth factor in fibrotic human liver and in activated hepatic stellate cells.J Hepatol 2000;32(5):754-61.
6. Murphy M,Godson C,Cannon S,Kato S,Mackenzie HS,Martin F,et al.Suppression subtractive hybridization identifies high glucose levels as a stimulus for expression of connective tissue growth factor and other genes in human mesangial cells.J Biol Chem 1999;274(9):5830-4.
7. Igarashi A,Okochi H,Bradham DM,Grotendorst GR.Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair.Mol Biol Cell 1993;4(6):637-45.
8. Brigstock DR,Steffen CL,Kim GY,Vegunta RK,Diehl JR,Harding PA.Purification and characterization of novel heparin-binding growth factors in uterine secretory fluids.Identification as heparin-regulated Mr 10,000 forms of connective tissue growth factor.J Biol Chem 1997;272(32):20275-82.
9. Fonseca C,Lindahl GE,Ponticos M,Sestini P,Renzoni EA,Holmes AM,et al.A polymorphism in the CTGF promoter region associated with systemic sclerosis.N Engl J Med 2007;357(12):1210-20.
10.Duncan MR,Frazier KS,Abramson S,Williams S,Klapper H,Huang X,et al.Connective tissue growth factor mediates transforming growth factor beta-induced collagen synthesis:down-regulation by cAMP.FASEB J 1999;13(13):1774-86.
11.Chaqour B,Goppelt-Struebe M.Mechanical regulation of the Cyr61/CCN1 and CTGF/CCN2 proteins.FEBS J 2006;273(16):3639-49.
12.Moussad EE,Brigstock DR.Connective tissue growth factor:what's in a name? Mol Genet Metab 2000;71(1-2):276-92.
13.Grotendorst GR,Okochi H,Hayashi N.A novel transforming growth factor beta response element controls the expression of the connective tissue growth factor gene.Cell Growth Differ 1996;7(4):469-80.
14.Gao R,Brigstock DR.Low density lipoprotein receptor-related protein(LRP)is a heparin-dependent adhesion receptor for connective tissue growth factor(CTGF)in rat activated hepatic stellate cells.Hepatol Res 2003;27(3):214-20.
15.Fu M,Zhang J,Zhu X,Myles DE,Willson TM,Liu X,et al.Peroxisome proliferator-activated receptor gamma inhibits transforming growth factor beta-induced connective tissue growth factor expression in human aortic smooth muscle cells by interfering with Smad3.J Biol Chem 2001;276(49):45888-94.
16.Chen Y,Segarini P,Raoufi F,Bradham D,Leask A.Connective tissue growth factor is secreted through the Golgi and is degraded in the endosome.Exp Cell Res 2001;271(1):109-17.
17.Ivkovic S,Yoon BS,Popoff SN,Safadi FF,Libuda DE,Stephenson RC,et al.Connective tissue growth factor coordinates chondrogenesis and angiogenesis during skeletal development.Development 2003;130(12):2779-91.
18.Murawaki Y,Ikuta Y,Koda M,Nishimura Y,Kawasaki H.Clinical significance of serum hyaluronan in patients with chronic viral liver disease.J Gastroenterol Hepatol 1996;11(5):459-65.
19.Kennedy L,Liu S,Shi-Wen X,Chen Y,Eastwood M,Sabetkar M,et al.CCN2 is necessary for the function of mouse embryonic fibroblasts.Exp Cell Res 2007;313(5):952-64.
20.Kothapalli D,Hayashi N,Grotendorst GR.Inhibition of TGF-beta-stimulated CTGF gene expression and anchorage-independent growth by cAMP identifies a CTGF-dependent restriction point in the cell cycle.FASEB J 1998;12(12):1151-61.
21.Gao R,Ball DK,Perbal B,Brigstock DR.Connective tissue growth factor induces c-fos gene activation and cell proliferation through p44/42 MAP kinase in primary rat hepatic stellate cells.J Hepatol 2004;40(3):431-8.
22.Song JJ,Aswad R,Kanaan RA,Rico MC,Owen TA,Barbe MF,et al.Connective tissue growth factor(CTGF)acts as a downstream mediator of TGF-betal to induce mesenchymal cell condensation.J Cell Physiol 2007;210(2):398-410.
23.Gao R,Brigstock DR.A novel integrin alpha5betal binding domain in module 4 of connective tissue growth factor(CCN2/CTGF)promotes adhesion and migration of activated pancreatic stellate cells.Gut 2006;55(6):856-62.
24.Korner T,Kropf J,Kosche B,Kristahl H,Jaspersen D,Gressner AM.Improvement of prognostic power of the Child-Pugh classification of liver cirrhosis by hyaluronan.J Hepatol 2003;39(6):947-53.
25.Wahab NA,Mason RM.A critical look at growth factors and epithelial-to-mesenchymal transition in the adult kidney.Interrelationships between growth factors that regulate EMT in the adult kidney.Nephron Exp Nephrol 2006;104(4).:e129-34.
26.Inoki I,Shiomi T,Hashimoto G,Enomoto H,Nakamura H,Makino K,et al.Connective tissue growth factor binds vascular endothelial growth factor(VEGF)and inhibits VEGF-induced angiogenesis.FASEB J 2002;16(2):219-21.
27.Lee JM,Dedhar S,Kalluri R,Thompson EW.The epithelial-mesenchymal transition:new insights in signaling,development,and disease.J Cell Biol 2006;172(7):973-81.
28.Kalluri R,Neilson EG.Epithelial-mesenchymal transition and its implications for fibrosis.J Clin Invest 2003;112(12):1776-84.
29.Neilson EG.Setting a trap for tissue fibrosis.Nat Med 2005;11(4):373-4.
30.Zavadil J,Cermak L,Soto-Nieves N,Bottinger ER Integration of TGF-beta/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition.EMBO J 2004;23(5):1155-65.
31.Abreu JG,Ketpura NI,Reversade B,De Robertis EM.Connective-tissue growth factor(CTGF)modulates cell signalling by BMP and TGF-beta.Nat Cell Biol 2002;4(8):599-604.
32.Zeisberg M,Hanai J,Sugimoto H,Mammoto T,Charytan D,Strutz F,et al.BMP-7 counteracts TGF-betal-induced epithelial-to-mesenchymal transition and reverses chronic renal injury.Nat Med 2003;9(7):964-8.
33.Wahab NA,Weston BS,Mason RM.Modulation of the TGFbeta/Smad signaling pathway in mesangial cells by CTGF/CCN2.Exp Cell Res 2005;307(2):305-14.
34.Lee EH,Joo CK.Role of transforming growth factor-beta in transdifferentiation and fibrosis of lens epithelial cells.Invest Ophthalmol Vis Sci 1999;40(9):2025-32.
35.van Setten GB,Blalock TD,Grotendorst G,Schultz GS.Detection of connective tissue growth factor in human aqueous humor.Ophthalmic Res 2002;34(5):306-8.
36.van Setten GB,Blalock TD,Grotendorst G,Schultz GS.Detection of connective tissue growth factor(CTGF)in human tear fluid:preliminary results.Acta Ophthalmol Scand 2003;81(1):51-3.
37.Ho SL,Dogar GF,Wang J,Crean J,Wu QD,Oliver N,et al.Elevated aqueous humour tissue inhibitor of matrix metalloproteinase-1 and connective tissue growth factor in pseudoexfoliation syndrome.Br J Ophthalmol 2005;89(2):169-73.
38.Razzaque MS,Foster CS,Ahmed AR.Role of connective tissue growth factor in the pathogenesis of conjunctival scarring in ocular cicatricial pemphigoid.Invest Ophthalmol Vis Sci 2003;44(5):1998-2003.
39.van Setten G,Aspiotis M,Blalock TD,Grotendorst G,Schultz G Connective tissue growth factor in pterygium:simultaneous presence with vascular endothelial growth factor-possible contributing factor to conjunctival scarring.Graefes Arch Clin Exp Ophthalmol 2003;241(2):135-9.
40.Wunderlich K,Senn BC,Reiser P,Pech M,Flammer J,Meyer P.Connective tissue growth factor in retrocorneal membranes and corneal scars.Ophthalmologica 2000;214(5):341-6.
41.Blalock TD,Duncan MR,Varela JC,Goldstein MH,Tuli SS,Grotendorst GR,et al.Connective tissue growth factor expression and action in human corneal fibroblast cultures and rat corneas after photorefractive keratectomy.Invest Ophthalmol Vis Sci 2003;44(5):1879-87.
42.Folger PA,Zekaria D,Grotendorst G,Masur SK.Transforming growth factor-beta-stimulated connective tissue growth factor expression during corneal myofibroblast differentiation.Invest Ophthalmol Vis Sci 2001;42(11):2534-41.
43.Huang Q,Hu YH,Zhang MC,Zhang Y.Induction of TGF-B1 on CTGF expression in cultured corneal fibroblasts.眼科新进展 2006;26(508-510).
44.Huang Q,Hu YH,Zhang MC,Zhang Y.Effects of amniotic membrane on expression of connective tissue growth factor and apoptosis of corneal f ibroblasts.眼科研究 2006;24(2).
45.Lama PJ,Fechtner RD.Antifibrotics and wound healing in glaucoma surgery.Surv Ophthalmol 2003;48(3):314-46.
46.Chudgar SM,Deng P,Maddala R,Epstein DL,Rao PV.Regulation of connective tissue growth factor expression in the aqueous humor outflow pathway.Mol Vis 2006;12:1117-26.
47.Wang YH,Hu YZ,Cao Y.TGF-B2 induces human Tenon's capsule fibroblasts to proliferate,express CTGF and fibronectin.Guoji Yanke Zazhi 2006;6(4).
48.Esson DW,Neelakantan A,Iyer SA,Blalock TD,Balasubramanian L,Grotendorst GR,et al.Expression of connective tissue growth factor after glaucoma filtration surgery in a rabbit model.Invest Ophthalmol Vis Sci 2004;45(2):485-91.
49.Yamanaka O,Saika S,Ikeda K,Miyazaki K,Kitano A,Ohnishi Y Connective tissue growth factor modulates extracellular matrix production in human subconjunctival fibroblasts and their proliferation and migration in vitro.Jpn J Ophthalmol 2008;52(1):8-15.
50.Wang JM,Hui N,Fan ZZ,Xiong L,Sun NX.Measurements of the filtering bleb area and intraocular pressure following subconjunctival injection of CTGF antibody after glaucoma filtration surgery in a rabbit model.Guoji Yanke Zazhi 2008;8(10).
51.Wunderlich K,Pech M,Eberle AN,Mihatsch M,Flammer J,Meyer P.Expression of connective tissue growth factor(CTGF)mRNA in plaques of human anterior subcapsular cataracts and membranes of posterior capsule opacification.Curr Eye Res 2000;21(2):627-36.
52.Park SK,Kim J,Seomun Y,Choi J,Kim DH,Han IO,et al.Hydrogen peroxide is a novel inducer of connective tissue growth factor.Biochem Biophys Res Commun 2001;284(4):966-71.
53.Bertelmann E,Kojetinsky C.Posterior capsule opacification and anterior capsule opacification.Curr Opin Ophthalmol 2001;12(1):35-40.
54.Marcantonio JM,Vrensen GF.Cell biology of posterior capsular opacification.Eye 1999;13(Pt 3b):484-8.
55.Mootha VV,Tesser R,Quails C.Incidence of and risk factors for residual posterior capsule opacification after cataract surgery.J Cataract Refract Surg 2004;30(11):2354-8.
56.Liu J,Hales AM,Chamberlain CG,McAvoy JW.Induction of cataract-like changes in rat lens epithelial explants by transforming growth factor beta.Invest Ophthalmol Vis Sci 1994;35(2):388-401.
57.Marcantonio JM,Syam PP,Liu CS,Duncan G.Epithelial transdifferentiation and cataract in the human lens.Exp Eye Res 2003;77(3):339-46.
58.Shirai K,Saika S,Okada Y,Oda S,Ohnishi Y Histology and immunohistochemistry of fibrous posterior capsule opacification in an infant.J Cataract Refract Surg 2004;30(2):523-6.
59.惠延年．玻璃体病．眼科学2004；第六版:162-8.
60.Hinton DR,He S,Jin ML,Barron E,Ryan SJ.Novel growth factors involved in the pathogenesis of proliferative vitreoretinopathy.Eye 2002;16(4):422-8.
61.Meyer P,Wunderlich K,Kain HL,Prunte C,Flammer J.Human connective tissue growth factor mRNA expression of epiretinal and subretinal fibrovascular membranes:a report of three cases.Ophthalmologica 2002;216(4):284-91.
62.Kuiper EJ,de Smet MD,van Meurs JC,Tan HS,Tanck MW,Oliver N,et al.Association of connective tissue growth factor with fibrosis in vitreoretinal disorders in the human eye.Arch Ophthalmol 2006;124(10):1457-62.
63.Abu El-Asrar AM,Van den Steen PE,Al-Amro SA,Missotten L,Opdenakker G,Geboes K.Expression of angiogenic and fibrogenic factors in proliferative vitreoretinal disorders.Int Ophthalmol 2007;27(1):11-22.
64.Cui JZ,Chiu A,Maberley D,Ma P,Samad A,Matsubara JA.Stage specificity of novel growth factor expression during development of proliferative vitreoretinopathy.Eye 2007;21(2):200-8.
65.Kita T,Hata Y,Kano K,Miura M,Nakao S,Noda Y,et al.Transforming growth factor-beta2 and connective tissue growth factor in proliferative vitreoretinal diseases:possible involvement of hyalocytes and therapeutic potential of Rho kinase inhibitor.Diabetes 2007;56(1):231-8.
66.Kita T,Hata Y,Miura M,Kawahara S,Nakao S,Ishibashi T.Functional characteristics of connective tissue growth factor on vitreoretinal cells.Diabetes 2007; 56(5):1421-8.
67.Guo Cm,Hui YN,Wang YS,Yan F.The correlation among connective tissue growth factor,tran sform ing growth factor-B receptor,and extracellular matr ix in human prol iferativemembranes of prol iferative v itreoretinopathy.Chin J Ocul Fundus Dis 2006;22(3):192-5.
68.Malone JI,Morrison AD,Pavan PR,Cuthbertson DD.Prevalence and significance of retinopathy in subjects with type 1 diabetes of less than 5 years' duration screened for the diabetes control and complications trial.Diabetes Care 2001;24(3):522-6.
69.Wunderlich K,Senn BC,Todesco L,Flammer J,Meyer P.Regulation of connective tissue growth factor gene expression in retinal vascular endothelial cells by angiogenic growth factors.Graefes Arch Clin Exp Ophthalmol 2000;238(11):910-5.
70.Hinton DR,Spee C,He S,Weitz S,Usinger W,LaBree L,et al.Accumulation of NH2-terminal fragment of connective tissue growth factor in the vitreous of patients with proliferative diabetic retinopathy.Diabetes Care 2004;27(3):758-64.
71.Kuiper EJ,Van Nieuwenhoven FA,de Smet MD,van Meurs JC,Tanck MW,Oliver N,et al.The angio-fibrotic switch of VEGF and CTGF in proliferative diabetic retinopathy.PLoS ONE 2008;3(7):e2675.
72.Kuiper EJ,Witmer AN,Klaassen I,Oliver N,Goldschmeding R,Schlingemann RO.Differential expression of connective tissue growth factor in microglia and pericytes in the human diabetic retina.Br J Ophthalmol 2004;88(8):1082-7.
73.Matsuda S,Gomi F,Katayama T,Koyama Y,Tohyama M,Tano Y.Induction of connective tissue growth factor in retinal pigment epithelium cells by oxidative stress.Jpn J Ophthalmol 2006;50(3):229-34.
74.Hughes JM,Kuiper EJ,Klaassen I,Canning P,Stitt AW,Van Bezu J,et al.Advanced glycation end products cause increased CCN family and extracellular matrix gene expression in the diabetic rodent retina.Diabetologia 2007;50(5):1089-98.
75.He S,Jin ML,Worpel V,Hinton DR.A role for connective tissue growth factor in the pathogenesis of choroidal neovascularization.Arch Ophthalmol 2003;121(9):1283-8.
2. Wormstone IM.Posterior capsule opacification:a cell biological perspective.Exp Eye Res 2002;74(3):337-47.
3. Taylor HR.Cataract:how much surgery do we have to do? Br J Ophthalmol 2000;84(1):1-2.
4. Dewey S.Posterior capsule opacification.Curr Opin Ophthalmol 2006;17(1):45-53.
5. Bertelmann E,Kojetinsky C.Posterior capsule opacification and anterior capsule opacification.Curr Opin Ophthalmol 2001;12(1):35-40.
6. Pandey SK,Apple DJ,Werner L,Maloof AJ,Milverton EJ.Posterior capsule opacification:a review of the aetiopathogenesis,experimental and clinical studies and factors for prevention.Indian J Ophthalmol 2004;52(2):99-112.
7. Aslam TM,Devlin H,Dhillon B.Use of Nd:YAG laser capsulotomy.Surv Ophthalmol 2003;48(6):594-612.
8. Bunting HJ,Laganowski H.Routine follow-up after YAG laser capsulotomy for posterior capsule opacification.Eye 2006;20(12):1449-50.
9. Billotte C,Berdeaux G.Adverse clinical consequences of neodymium:YAG laser treatment of posterior capsule opacification.J Cataract.Refract Surg 2004;30(10):2064-71.
10. Apple DJ,Solomon KD,Tetz MR,Assia EI,Holland EY,Legler UF,Tsai JC,Castaneda VE,Hoggatt JP,Kostick AM.Posterior capsule opacification.Surv Ophthalmol 1992;37(2):73-116.
11. Wormstone IM,Wang L,Liu CS.Posterior capsule opacification.Exp Eye Res 2009;88(2):257-69.
12. Gordon-Thomson C,de Iongh RU,Hales AM,Chamberlain CG,McAvoy JW.Differential cataractogenic potency of TGF-betal,-beta2,and-beta3 and their expression in the postnatal rat eye.Invest Ophthalmol Vis Sci 1998;39(8):1399-409.
13. Shirai K,Saika S,Okada Y,Oda S,Ohnishi Y.Histology and immunohistochemistry of fibrous posterior capsule opacification in an infant.J Cataract Refract Surg 2004;30(2):523-6.
14. de Iongh RU,Wederell E,Lovicu FJ,McAvoy JW.Transforming growth factor-beta-induced epithelial-mesenchymal transition in the lens:a model for cataract formation.Cells Tissues Organs 2005;179(1-2):43-55.
15. de Iongh RU,Gordon-Thomson C,Chamberlain CG,Hales AM,McAvoy JW.Tgfbeta receptor expression in lens:implications for differentiation and cataractogenesis.Exp Eye Res 2001;72(6):649-59.
16. Jampel HD,Roche N,Stark WJ,Roberts AB.Transforming growth factor-beta in human aqueous humor.Curr Eye Res 1990;9(10):963-9.
17. Dawes LJ,Eldred JA,Anderson IK,Sleeman M,Reddan JR,Duncan G,Wormstone IM.TGF beta-induced contraction is not promoted by fibronectin-fibronectin receptor interaction,or alpha SMA expression.Invest Ophthalmol Vis Sci 2008;49(2):650-61.
18. Yao K,Ye PP,Tan J,Tang XJ,Shen Tu XC.Involvement of PI3K/Akt pathway in TGF-beta2-mediated epithelial mesenchymal transition in human lens epithelial cells.Ophthalmic Res 2008;40(2):69-76.
19. Yao K,Tan J,Ye P,Wang K,Xu W,ShenTu X,Tang X.Integrin betal-mediated signaling is involved in transforming growth factor-beta2-promoted migration in human lens epithelial cells.Mol Vis 2007;13:1769-76.
20. Yao K,Tan J,Gu WZ,Ye PP,Wang KJ.Reactive oxygen species mediates the apoptosis induced by transforming growth factor beta(2)in human lens epithelial cells.Biochem Biophys Res Commun 2007;354(1):278-83.
21. Bradham DM,Igarashi A,Potter RL,Grotendorst GR.Connective tissue growth factor:a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10.J Cell Biol 1991;114(6):1285-94.
22. Williams EJ,Gaca MD,Brigstock DR,Arthur MJ,Benyon RC.Increased expression of connective tissue growth factor in fibrotic human liver and in activated hepatic stellate cells.J Hepatol 2000;32(5):754-61.
23. Murphy M,Godson C,Cannon S,Kato S,Mackenzie HS,Martin F,Brady HR.Suppression subtractive hybridization identifies high glucose levels as a stimulus for expression of connective tissue growth factor and other genes in human mesangial cells.J Biol Chem 1999;274(9):5830-4.
24. Igarashi A,Okochi H,Bradham DM,Grotendorst GR.Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair.Mol Biol Cell 1993;4(6):637-45.
25. Rachfal AW,Brigstock DR.Structural and functional properties of CCN proteins.Vitam Horm 2005;70:69-103.
26. Moussad EE,Brigstock DR.Connective tissue growth factor:what's in a name? Mol Genet Metab 2000;71(1-2):276-92.
27. Kothapalli D,Hayashi N,Grotendorst GR.Inhibition of TGF-beta-stimulated CTGF gene expression and anchorage-independent growth by cAMP identifies a CTGF-dependent restriction point in the cell cycle.FASEB J 1998;12(12):1151-61.
28. Gao R,Ball DK,Perbal B,Brigstock DR.Connective tissue growth factor induces c-fos gene activation and cell proliferation through p44/42 MAP kinase in primary rat hepatic stellate cells.J Hepatol 2004;40(3):431-8.
29. Song JJ,Aswad R,Kanaan RA,Rico MC,Owen TA,Barbe MF,Safadi FF, Popoff SN.Connective tissue growth factor(CTGF)acts as a downstream mediator of TGF-betal to induce mesenchymal cell condensation.J Cell Physiol 2007;210(2):398-410.
30. Gao R,Brigstock DR.A novel integrin alpha5betal binding domain in module 4 of connective tissue growth factor(CCN2/CTGF)promotes adhesion and migration of activated pancreatic stellate cells.Gut 2006;55(6):856-62.
31. Korner T,Kropf J,Kosche B,Kristahl H,Jaspersen D,Gressner AM.Improvement of prognostic power of the Child-Pugh classification of liver cirrhosis by hyaluronan.J Hepatol 2003;39(6):947-53.
32. Wahab NA,Mason RM.A critical look at growth factors and epithelial-to-mesenchymal transition in the adult kidney.Interrelationships between growth factors that regulate EMT in the adult kidney.Nephron Exp Nephrol 2006;104(4):e129-34.
33. Lee EH,Joo CK.Role of transforming growth factor-beta in transdifferentiation and fibrosis of lens epithelial cells.Invest Ophthalmol Vis Sci 1999;40(9):2025-32.
34. Wunderlich K,Pech M,Eberle AN,Mihatsch M,Flammer J,Meyer P.Expression of connective tissue growth factor(CTGF)mRNA in plaques of human anterior subcapsular cataracts and membranes of posterior capsule opacification.Curr Eye Res 2000;21(2):627-36.
35. Wormstone IM,Tamiya S,Eldred JA,Lazaridis K,Chantry A,Reddan JR,Anderson I,Duncan G.Characterisation of TGF-beta2 signalling and function in a human lens cell line.Exp Eye Res 2004;78(3):705-14.
36. Garrett Q,Khaw PT,Blalock TD,Schultz GS,Grotendorst GR,Daniels JT.Involvement of CTGF in TGF-betal-stimulation of myofibroblast differentiation and collagen matrix contraction in the presence of mechanical stress.Invest Ophthalmol Vis Sci 2004;45(4):1109-16.
37. Elbashir SM,Martinez J,Patkaniowska A,Lendeckel W,Tuschl T.Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate.EMBO J 2001;20(23):6877-88.
38. Zhou HJ,Tsai SY,Tsai MJ.RNAi technology and its use in studying the function of nuclear receptors and coregulators.Nucl Recept Signal 2003;1:e008.
39. Donze O,Picard D.RNA interference in mammalian cells using siRNAs synthesized with T7 RNA polymerase.Nucleic Acids Res 2002;30(10):e46.
40. Fire A,Xu S,Montgomery MK,Kostas SA,Driver SE,Mello CC.Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans.Nature 1998;391(6669):806-1
1.Bradham DM,Igarashi A,Potter RL,Grotendorst GR.Connective tissue growth factor:a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10.J Cell Biol 1991;114(6):1285-94.
2. Williams EJ,Gaca MD,Brigstock DR,Arthur MJ,Benyon RC.Increased expression of connective tissue growth factor in fibrotic human liver and in activated hepatic stellate cells.J Hepatol 2000;32(5):754-61.
3. Murphy M,Godson C,Cannon S,Kato S,Mackenzie HS,Martin F,et al.Suppression subtractive hybridization identifies high glucose levels as a stimulus for expression of connective tissue growth factor and other genes in human mesangial cells.J Biol Chem 1999;274(9):5830-4.
4. Igarashi A,Okochi H,Bradham DM,Grotendorst GR.Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair.Mol Biol Cell 1993;4(6):637-45.
5. Lee EH,Joo CK.Role of transforming growth factor-beta in transdifferentiation and fibrosis of lens epithelial cells.Invest Ophthalmol Vis Sci 1999;40(9):2025-32.
6. van Setten GB,Blalock TD,Grotendorst G,Schultz GS.Detection of connective tissue growth factor in human aqueous humor.Ophthalmic Res 2002;34(5):306-8.
7. van Setten GB,Blalock TD,Grotendorst G,Schultz GS.Detection of connective tissue growth factor(CTGF)in human tear fluid:preliminary results.Acta Ophthalmol Scand 2003;81(1):51-3.
8. Ho SL,Dogar GE,Wang J,Crean J,Wu QD,Oliver N,et al.Elevated aqueous humour tissue inhibitor of matrix metalloproteinase-1 and connective tissue growth factor in pseudoexfoliation syndrome.Br J Ophthalmol 2005;89(2):169-73.
9. Wunderlich K,Pech M,Eberle AN,Mihatsch M,Flammer J,Meyer P.Expression of connective tissue growth factor(CTGF)mRNA in plaques of human anterior subcapsular cataracts and membranes of posterior capsule opacification.Curr Eye Res 2000;21(2):627-36.
10.Wormstone IM,Tamiya S,Eldred JA,Lazaridis K,Chantry A,Reddan JR,et al.Characterisation of TGF-beta2 signalling and function in a human lens cell line.Exp Eye Res 2004;78(3):705-14.
11.Andley UP,Rhim JS,Chylack LT,Jr.,Fleming TP.Propagation and immortalization of human lens epithelial cells in culture.Invest Ophthalmol Vis Sci 1994;35(7):3094-102.
12.Yao K,Ye PP,Tan J,Tang XJ,Shen Tu XC.Involvement of PI3K/Akt pathway in TGF-beta2-mediated epithelial mesenchymal transition in human lens epithelial cells.Ophthalmic Res 2008;40(2):69-76.
13.Massague J.The transforming growth factor-beta family.Annu Rev Cell Biol 1990;6:597-641.
14.Saika S.TGFbeta pathobiology in the eye.Lab Invest 2006;86(2):106-15.
15.Yao K,Tan J,Ye P,Wang K,Xu W,ShenTu X,et al.Integrin betal-mediated signaling is involved in transforming growth factor-beta2-promoted migration in human lens epithelial cells.Mol Vis 2007;13:1769-76.
16.Yao K,Tan J,Gu WZ,Ye PP,Wang KJ.Reactive oxygen species mediates the apoptosis induced by transforming growth factor beta(2)in human lens epithelial cells.Biochem Biophys Res Commun 2007;354(1):278-83.
17.Wahab NA,Brinkman H,Mason RM.Uptake and intracellular transport of the connective tissue growth factor:a potential mode of action.Biochem J 2001;359(Pt 1):89-97.
18.Chen Y,Segarini P,Raoufi F,Bradham D,Leask A.Connective tissue growth factor is secreted through the Golgi and is degraded in the endosome.Exp Cell Res 2001; 271(1):109-17.
19.Dziadzio M,Usinger W,Leask A,Abraham D,Black CM,Denton C,et al.N-terminal connective tissue growth factor is a marker of the fibrotic phenotype in scleroderma.QJM 2005;98(7):485-92.
20.Okamura M,Yamaji S,Nagashima Y,Nishikawa M,Yoshimoto N,Kido Y,et al.Prognostic value of integrin betal-ILK-pAkt signaling pathway in non-small cell lung cancer.Hum Pathol 2007;38(7):1081-91.
21.Mori T,Kawara S,Shinozaki M,Hayashi N,Kakinuma T,Igarashi A,et al.Role and interaction of connective tissue growth factor with transforming growth factor-beta in persistent fibrosis:A mouse fibrosis model.J Cell Physiol 1999;181(1):153-9.
22.Burns WC,Twigg SM,Forbes JM,Pete J,Tikellis C,Thallas-Bonke V,et al.Connective tissue growth factor plays an important role in advanced glycation end product-induced tubular epithelial-to-mesenchymal transition:implications for diabetic renal disease.J Am Soc Nephrol 2006;17(9):2484-94.
23.Song JJ,Aswad R,Kanaan RA,Rico MC,Owen TA,Barbe MF,et al.Connective tissue growth factor(CTGF)acts as a downstream mediator of TGF-betal to induce mesenchymal cell condensation.J Cell Physiol 2007;210(2):398-410.
24.Arnott JA,Nuglozeh E,Rico MC,Arango-Hisijara I,Odgren PR,Safadi FF,et al.Connective tissue growth factor(CTGF/CCN2)is a downstream mediator for TGF-b1-induced extracellular matrix production in osteoblasts.Jounal of cellular physiology 2007;210:843-52.
25.Ihn H.Pathogenesis of fibrosis:role of TGF-beta and CTGF.Curr Opin Rheumatol 2002;14(6):681-5.
26.Grotendorst GR,Okochi H,Hayashi N.A novel transforming growth factor beta response element controls the expression of the connective tissue growth factor gene.Cell Growth Differ 1996;7(4):469-80.
27.Leask A,Holmes A,Black CM,Abraham DJ.Connective tissue growth factor gene regulation.Requirements for its induction by transforming growth factor-beta 2 in fibroblasts.J Biol Chem 2003;278(15):13008-15.
28.Holmes A,Abraham DJ,Sa S,Shiwen X,Black CM,Leask A.CTGF and SMADs,maintenance of scleroderma phenotype is independent of SMAD signaling.J Biol Chem 2001;276(14):10594-601.
29.Samarakoon R,Higgins CE,Higgins SP,Higgins PJ.Differential requirement for MEK/ERK and SMAD signaling in PAI-1 and CTGF expression in response to microtubule disruption.Cell Signal 2009;21(6):986-95.
30.Secker GA,Shortt AJ,Sampson E,Schwarz QP,Schultz GS,Daniels JT.TGFbeta stimulated re-epithelialisation is regulated by CTGF and Ras/MEK/ERK signalling.Exp Cell Res 2008;314(1):131-42.
31.Yosimichi G,Kubota S,Nishida T,Kondo S,Yanagita T,Nakao K,et al.Roles of PKC,PI3K and JNK in multiple transduction of CCN2/CTGF signals in chondrocytes.Bone 2006;38(6):853-63.
32.Chen Y,Blom IE,Sa S,Goldschmeding R,Abraham DJ,Leask A.CTGF expression in mesangial cells:involvement of SMADs,MAP kinase,and PKC.Kidney Int 2002;62(4):1149-59.
1. Apple DJ,Solomon KD,Tetz MR,Assia EI,Holland EY,Legler UF,et al.Posterior capsule opacification.Surv Ophthalmol 1992;37(2):73-116.
2. Apple DJ,Peng Q,Visessook N,Werner L,Pandey SK,Escobar-Gomez M,et al.Eradication of posterior capsule opacification:documentation of a marked decrease in Nd:YAG laser posterior capsulotomy rates noted in an analysis of 5416 pseudophakic human eyes obtained postmortem.Ophthalmology 2001;108(3):505-18.
3. Hutchinson AK,Wilson ME,Saunders RA.Outcomes and ocular growth rates after intraocular lens implantation in the first 2 years of life.J Cataract Refract Surg 1998;24(6):846-52.
4. Fagerholm P,Lundevall E,Trocme S,Wroblewski R.Human and experimental lens repair and calcification.Exp Eye Res 1986;43(6):965-72.
5. Prakash G,Jhanji V,Sharma N,Titiyal JS.Posterior capsule opacification in diabetic patients.J Cataract Refract Surg 2007;33(3):363-4.
6. Bras ID,Colitz CM,Saville WJ,Gemensky-Metzler AJ,Wilkie DA.Posterior capsular opacification in diabetic and nondiabetic canine patients following cataract surgery.Vet Ophthalmol 2006;9(5):317-27.
7. Aslam TM,Devlin H,Dhillon B.Use of Nd:YAG laser capsulotomy.Surv Ophthalmol 2003;48(6):594-612.
8. Bunting HJ,Laganowski H.Routine follow-up after YAG laser capsulotomy for posterior capsule opacification.Eye 2006;20(12):1449-50.
9. Billotte C,Berdeaux G.Adverse clinical consequences of neodymium:YAG laser treatment of posterior capsule opacification.J Cataract Refract Surg 2004;30(10):2064-71.
10.Lee JM,Dedhar S,Kalluri R,Thompson EW.The epithelial-mesenchymal transition:new insights in signaling,development,and disease.J Cell Biol 2006; 172(7):973-81.
11.Lovicu FJ,Schulz MW,Hales AM,Vincent LN,Overbeek PA,Chamberlain CG,et al.TGFbeta induces morphological and molecular changes similar to human anterior subcapsular cataract.Br J Ophthalmol 2002;86(2):220-6.
12.Marcantonio JM,Syam PP,Liu CS,Duncan G Epithelial transdifferentiation and cataract in the human lens.Exp Eye Res 2003;77(3):339-46.
13.Shirai K,Saika S,Okada Y,Oda S,Ohnishi Y.Histology and immunohistochemistry of fibrous posterior capsule opacification in an infant.J Cataract Refract Surg 2004;30(2):523-6.
14.Zavadil J,Cermak L,Soto-Nieves N,Bottinger EP.Integration of TGF-beta/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition.EMBO J 2004;23(5):1155-65.
15.Wahab NA,Weston BS,Mason RM.Modulation of the TGFbeta/Smad signaling pathway in mesangial cells by CTGF/CCN2.Exp Cell Res 2005;307(2):305-14.
16.Wahab NA,Mason RM.A critical look at growth factors and epithelial-to-mesenchymal transition in the adult kidney.Interrelationships between growth factors that regulate EMT in the adult kidney.Nephron Exp Nephrol 2006;104(4):e129-34.
17.Zeisberg M,Hanai J,Sugimoto H,Mammoto T,Charytan D,Strutz F,et al.BMP-7 counteracts TGF-betal-induced epithelial-to-mesenchymal transition and reverses chronic renal injury.Nat Med 2003;9(7):964-8.
18.Abreu JG,Ketpura NI,Reversade B,De Robertis EM.Connective-tissue growth factor(CTGF)modulates cell signalling by BMP and TGF-beta.Nat Cell Biol 2002;4(8):599-604.
19.Gore-Hyer E,Shegogue D,Markiewicz M,Lo S,Hazen-Martin D,Greene EL,et al.TGF-beta and CTGF have overlapping and distinct fibrogenic effects on human renal cells.Am J Physiol Renal Physiol 2002;283(4):F707-16.
20.Weston BS,Wahab NA,Mason RM.CTGF mediates TGF-beta-induced fibronectin matrix deposition by upregulating active alpha5betal integrin in human mesangial cells.J Am Soc Nephrol 2003;14(3):601-10.
21.Leask A.Transcriptional profiling of the scleroderma fibroblast reveals a potential role for connective tissue growth factor(CTGF)in pathological fibrosis.Keio J Med 2004;53(2):74-7.
22.Yao K,Tan J,Gu WZ,Ye PP,Wang KJ.Reactive oxygen species mediates the apoptosis induced by transforming growth factor beta(2)in human lens epithelial cells.Biochem Biophys Res Commun 2007;354(1):278-83.
23.Yao K,Tan J,Ye P,Wang K,Xu W,ShenTu X,et al.Integrin betal-mediated signaling is involved in transforming growth factor-beta2-promoted migration in human lens epithelial cells.Mol Vis 2007;13:1769-76.
24.Yao K,Ye PP,Tan J,Tang XJ,Shen Tu XC.Involvement of PI3K/AM pathway in TGF-beta2-mediated epithelial mesenchymal transition in human lens epithelial cells.Ophthalmic Res 2008;40(2):69-76.
25.Awasthi N,Wagner BJ.Suppression of human lens epithelial cell proliferation by proteasome inhibition,a potential defense against posterior capsular opacification.Invest Ophthalmol Vis Sci 2006;47(10):4482-9.
26.Donaldson PJ,Roos M,Evans C,Beyer E,Kistler J.Electrical properties of mammalian lens epithelial gap junction channels.Invest Ophthalmol Vis Sci 1994;35(9):3422-8.
27.Gupta VK,Berthoud VM,Atal N,Jarillo JA,Barrio LC,Beyer EC.Bovine connexin44,a lens gap junction protein:molecular cloning,immunologic characterization,and functional expression.Invest Ophthalmol Vis Sci 1994;35(10):3747-58.
28.Gu S,Yu XS,Yin X,Jiang JX.Stimulation of lens cell differentiation by gap junction protein connexin 45.6.Invest Ophthalmol Vis Sci 2003;44(5):2103-11.
29.Le AC,Musil LS.A novel role for FGF and extracellular signal-regulated kinase in gap junction-mediated intercellular communication in the lens.J Cell Biol 2001;154(1):197-216.
30.Lovicu FJ,Steven P,Saika S,McAvoy JW.Aberrant lens fiber differentiation in anterior subcapsular cataract formation:a process dependent on reduced levels of Pax6.Investigative ophthalmology & visual science 2004;45(6):1946-53.
31.Krutovskikh VA,Troyanovsky SM,Piccoli C,Tsuda H,Asamoto M,Yamasaki H.Differential effect of subcellular localization of communication impairing gap junction protein connexin43 on tumor cell growth in vivo.Oncogene 2000;19(4):505-13.
32.Maass K,Shibayama J,Chase SE,Willecke K,Delmar M.C-terminal truncation of connexin43 changes number,size,and localization of cardiac gap junction plaques.Circ Res 2007;101(12):1283-91.
33.Xie H,Laird DW,Chang TH,Hu VW.A mitosis-specific phosphorylation of the gap junction protein connexin43 in human vascular cells:biochemical characterization and localization.J Cell Biol 1997;137(1):203-10.
34.Fatigati V,Murphy RA.Actin and tropomyosin variants in smooth muscles.Dependence on tissue type.J Biol Chem 1984;259(23):14383-8.
35.Cobo LM,Ohsawa E,Chandler D,Arguello R,George G.Pathogenesis of capsular opacification after extracapsular cataract extraction.An animal model.Ophthalmology 1984;91(7):857-63.
36.de Iongh RU,Wederell E,Lovicu FJ,McAvoy JW.Transforming growth factor-beta-induced epithelial-mesenchymal transition in the lens:a model for cataract formation.Cells Tissues Organs 2005;179(1-2):43-55.
37.Lee EH,Joo CK.Role of transforming growth factor-beta in transdifferentiation and fibrosis of lens epithelial cells.Invest Ophthalmol Vis Sci 1999;40(9):2025-32.
38.Hannigan GE,Leung-Hagesteijn C,Fitz-Gibbon L,Coppolino MG,Radeva G,Filmus J,et al.Regulation of cell adhesion and anchorage-dependent growth by a new beta 1-integrin-linked protein kinase.Nature 1996;379(6560):91-6.
39.Weaver MS,Toida N,Sage EH.Expression of integrin-linked kinase in the murine lens is consistent with its role in epithelial-mesenchymal transition of lens epithelial cells in vitro.Mol Vis 2007;13:707-18.
40.van Setten GB,Blalock TD,Grotendorst G,Schultz GS.Detection of connective tissue growth factor in human aqueous humor.Ophthalmic Res 2002;34(5):306-8.
41.Ho SL,Dogar GF,Wang J,Crean J,Wu QD,Oliver N,et al.Elevated aqueous humour tissue inhibitor of matrix metalloproteinase-1 and connective tissue growth factor in pseudoexfoliation syndrome.Br J Ophthalmol 2005;89(2):169-73.
42.Grotendorst GR,Okochi H,Hayashi N.A novel transforming growth factor beta response element controls the expression of the connective tissue growth factor gene.Cell Growth Differ 1996;7(4):469-80.
43.Olivero DK,Furcht LT.Type IV collagen,laminin,and fibronectin promote the adhesion and migration of rabbit lens epithelial cells in vitro.Invest Ophthalmol Vis Sci 1993;34(10):2825-34.
44.Negash S,Wang HS,Gao C,Ledee D,Zelenka P.Cdk5 regulates cell-matrix and cell-cell adhesion in lens epithelial cells.J Cell Sci 2002;115(Pt 10):2109-17.
45.Weaver MS,Sage EH,Yan Q.Absence of SPARC in lens epithelial cells results in altered adhesion and extracellular matrix production in vitro.J Cell Biochem 2006;97(2):423-32.
46.Schlaepfer DD,Hanks SK,Hunter T,van der Geer P.Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase.Nature 1994;372(6508):786-91.
47.Richardson A,Parsons JT.Signal transduction through integrins:a central role for focal adhesion kinase.Bioessays 1995;17(3):229-36.
48.Schlaepfer DD,Hauck CR,Sieg DJ.Signaling through focal adhesion kinase.Prog Biophys Mol Biol 1999;71(3-4):435-78.
1. Bradham DM,Igarashi A,Potter RL,Grotendorst GR.Connective tissue growth factor:a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10.J Cell Biol 1991;114(6):1285-94.
2. Leask A,Abraham DJ.All in the CCN family:essential matricellular signaling modulators emerge from the bunker.J Cell Sci 2006;119(Pt 23):4803-10.
3. Rachfal AW,Brigstock DR.Structural and functional properties of CCN proteins.Vitam Horm 2005;70:69-103.
4. Bork P.The modular architecture of a new family of growth regulators related to connective tissue growth factor.FEBS Lett 1993;327(2):125-30.
5. Williams EJ,Gaca MD,Brigstock DR,Arthur MJ,Benyon RC.Increased expression of connective tissue growth factor in fibrotic human liver and in activated hepatic stellate cells.J Hepatol 2000;32(5):754-61.
6. Murphy M,Godson C,Cannon S,Kato S,Mackenzie HS,Martin F,et al.Suppression subtractive hybridization identifies high glucose levels as a stimulus for expression of connective tissue growth factor and other genes in human mesangial cells.J Biol Chem 1999;274(9):5830-4.
7. Igarashi A,Okochi H,Bradham DM,Grotendorst GR.Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair.Mol Biol Cell 1993;4(6):637-45.
8. Brigstock DR,Steffen CL,Kim GY,Vegunta RK,Diehl JR,Harding PA.Purification and characterization of novel heparin-binding growth factors in uterine secretory fluids.Identification as heparin-regulated Mr 10,000 forms of connective tissue growth factor.J Biol Chem 1997;272(32):20275-82.
9. Fonseca C,Lindahl GE,Ponticos M,Sestini P,Renzoni EA,Holmes AM,et al.A polymorphism in the CTGF promoter region associated with systemic sclerosis.N Engl J Med 2007;357(12):1210-20.
10.Duncan MR,Frazier KS,Abramson S,Williams S,Klapper H,Huang X,et al.Connective tissue growth factor mediates transforming growth factor beta-induced collagen synthesis:down-regulation by cAMP.FASEB J 1999;13(13):1774-86.
11.Chaqour B,Goppelt-Struebe M.Mechanical regulation of the Cyr61/CCN1 and CTGF/CCN2 proteins.FEBS J 2006;273(16):3639-49.
12.Moussad EE,Brigstock DR.Connective tissue growth factor:what's in a name? Mol Genet Metab 2000;71(1-2):276-92.
13.Grotendorst GR,Okochi H,Hayashi N.A novel transforming growth factor beta response element controls the expression of the connective tissue growth factor gene.Cell Growth Differ 1996;7(4):469-80.
14.Gao R,Brigstock DR.Low density lipoprotein receptor-related protein(LRP)is a heparin-dependent adhesion receptor for connective tissue growth factor(CTGF)in rat activated hepatic stellate cells.Hepatol Res 2003;27(3):214-20.
15.Fu M,Zhang J,Zhu X,Myles DE,Willson TM,Liu X,et al.Peroxisome proliferator-activated receptor gamma inhibits transforming growth factor beta-induced connective tissue growth factor expression in human aortic smooth muscle cells by interfering with Smad3.J Biol Chem 2001;276(49):45888-94.
16.Chen Y,Segarini P,Raoufi F,Bradham D,Leask A.Connective tissue growth factor is secreted through the Golgi and is degraded in the endosome.Exp Cell Res 2001;271(1):109-17.
17.Ivkovic S,Yoon BS,Popoff SN,Safadi FF,Libuda DE,Stephenson RC,et al.Connective tissue growth factor coordinates chondrogenesis and angiogenesis during skeletal development.Development 2003;130(12):2779-91.
18.Murawaki Y,Ikuta Y,Koda M,Nishimura Y,Kawasaki H.Clinical significance of serum hyaluronan in patients with chronic viral liver disease.J Gastroenterol Hepatol 1996;11(5):459-65.
19.Kennedy L,Liu S,Shi-Wen X,Chen Y,Eastwood M,Sabetkar M,et al.CCN2 is necessary for the function of mouse embryonic fibroblasts.Exp Cell Res 2007;313(5):952-64.
20.Kothapalli D,Hayashi N,Grotendorst GR.Inhibition of TGF-beta-stimulated CTGF gene expression and anchorage-independent growth by cAMP identifies a CTGF-dependent restriction point in the cell cycle.FASEB J 1998;12(12):1151-61.
21.Gao R,Ball DK,Perbal B,Brigstock DR.Connective tissue growth factor induces c-fos gene activation and cell proliferation through p44/42 MAP kinase in primary rat hepatic stellate cells.J Hepatol 2004;40(3):431-8.
22.Song JJ,Aswad R,Kanaan RA,Rico MC,Owen TA,Barbe MF,et al.Connective tissue growth factor(CTGF)acts as a downstream mediator of TGF-betal to induce mesenchymal cell condensation.J Cell Physiol 2007;210(2):398-410.
23.Gao R,Brigstock DR.A novel integrin alpha5betal binding domain in module 4 of connective tissue growth factor(CCN2/CTGF)promotes adhesion and migration of activated pancreatic stellate cells.Gut 2006;55(6):856-62.
24.Korner T,Kropf J,Kosche B,Kristahl H,Jaspersen D,Gressner AM.Improvement of prognostic power of the Child-Pugh classification of liver cirrhosis by hyaluronan.J Hepatol 2003;39(6):947-53.
25.Wahab NA,Mason RM.A critical look at growth factors and epithelial-to-mesenchymal transition in the adult kidney.Interrelationships between growth factors that regulate EMT in the adult kidney.Nephron Exp Nephrol 2006;104(4).:e129-34.
26.Inoki I,Shiomi T,Hashimoto G,Enomoto H,Nakamura H,Makino K,et al.Connective tissue growth factor binds vascular endothelial growth factor(VEGF)and inhibits VEGF-induced angiogenesis.FASEB J 2002;16(2):219-21.
27.Lee JM,Dedhar S,Kalluri R,Thompson EW.The epithelial-mesenchymal transition:new insights in signaling,development,and disease.J Cell Biol 2006;172(7):973-81.
28.Kalluri R,Neilson EG.Epithelial-mesenchymal transition and its implications for fibrosis.J Clin Invest 2003;112(12):1776-84.
29.Neilson EG.Setting a trap for tissue fibrosis.Nat Med 2005;11(4):373-4.
30.Zavadil J,Cermak L,Soto-Nieves N,Bottinger ER Integration of TGF-beta/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition.EMBO J 2004;23(5):1155-65.
31.Abreu JG,Ketpura NI,Reversade B,De Robertis EM.Connective-tissue growth factor(CTGF)modulates cell signalling by BMP and TGF-beta.Nat Cell Biol 2002;4(8):599-604.
32.Zeisberg M,Hanai J,Sugimoto H,Mammoto T,Charytan D,Strutz F,et al.BMP-7 counteracts TGF-betal-induced epithelial-to-mesenchymal transition and reverses chronic renal injury.Nat Med 2003;9(7):964-8.
33.Wahab NA,Weston BS,Mason RM.Modulation of the TGFbeta/Smad signaling pathway in mesangial cells by CTGF/CCN2.Exp Cell Res 2005;307(2):305-14.
34.Lee EH,Joo CK.Role of transforming growth factor-beta in transdifferentiation and fibrosis of lens epithelial cells.Invest Ophthalmol Vis Sci 1999;40(9):2025-32.
35.van Setten GB,Blalock TD,Grotendorst G,Schultz GS.Detection of connective tissue growth factor in human aqueous humor.Ophthalmic Res 2002;34(5):306-8.
36.van Setten GB,Blalock TD,Grotendorst G,Schultz GS.Detection of connective tissue growth factor(CTGF)in human tear fluid:preliminary results.Acta Ophthalmol Scand 2003;81(1):51-3.
37.Ho SL,Dogar GF,Wang J,Crean J,Wu QD,Oliver N,et al.Elevated aqueous humour tissue inhibitor of matrix metalloproteinase-1 and connective tissue growth factor in pseudoexfoliation syndrome.Br J Ophthalmol 2005;89(2):169-73.
38.Razzaque MS,Foster CS,Ahmed AR.Role of connective tissue growth factor in the pathogenesis of conjunctival scarring in ocular cicatricial pemphigoid.Invest Ophthalmol Vis Sci 2003;44(5):1998-2003.
39.van Setten G,Aspiotis M,Blalock TD,Grotendorst G,Schultz G Connective tissue growth factor in pterygium:simultaneous presence with vascular endothelial growth factor-possible contributing factor to conjunctival scarring.Graefes Arch Clin Exp Ophthalmol 2003;241(2):135-9.
40.Wunderlich K,Senn BC,Reiser P,Pech M,Flammer J,Meyer P.Connective tissue growth factor in retrocorneal membranes and corneal scars.Ophthalmologica 2000;214(5):341-6.
41.Blalock TD,Duncan MR,Varela JC,Goldstein MH,Tuli SS,Grotendorst GR,et al.Connective tissue growth factor expression and action in human corneal fibroblast cultures and rat corneas after photorefractive keratectomy.Invest Ophthalmol Vis Sci 2003;44(5):1879-87.
42.Folger PA,Zekaria D,Grotendorst G,Masur SK.Transforming growth factor-beta-stimulated connective tissue growth factor expression during corneal myofibroblast differentiation.Invest Ophthalmol Vis Sci 2001;42(11):2534-41.
43.Huang Q,Hu YH,Zhang MC,Zhang Y.Induction of TGF-B1 on CTGF expression in cultured corneal fibroblasts.眼科新进展 2006;26(508-510).
44.Huang Q,Hu YH,Zhang MC,Zhang Y.Effects of amniotic membrane on expression of connective tissue growth factor and apoptosis of corneal f ibroblasts.眼科研究 2006;24(2).
45.Lama PJ,Fechtner RD.Antifibrotics and wound healing in glaucoma surgery.Surv Ophthalmol 2003;48(3):314-46.
46.Chudgar SM,Deng P,Maddala R,Epstein DL,Rao PV.Regulation of connective tissue growth factor expression in the aqueous humor outflow pathway.Mol Vis 2006;12:1117-26.
47.Wang YH,Hu YZ,Cao Y.TGF-B2 induces human Tenon's capsule fibroblasts to proliferate,express CTGF and fibronectin.Guoji Yanke Zazhi 2006;6(4).
48.Esson DW,Neelakantan A,Iyer SA,Blalock TD,Balasubramanian L,Grotendorst GR,et al.Expression of connective tissue growth factor after glaucoma filtration surgery in a rabbit model.Invest Ophthalmol Vis Sci 2004;45(2):485-91.
49.Yamanaka O,Saika S,Ikeda K,Miyazaki K,Kitano A,Ohnishi Y Connective tissue growth factor modulates extracellular matrix production in human subconjunctival fibroblasts and their proliferation and migration in vitro.Jpn J Ophthalmol 2008;52(1):8-15.
50.Wang JM,Hui N,Fan ZZ,Xiong L,Sun NX.Measurements of the filtering bleb area and intraocular pressure following subconjunctival injection of CTGF antibody after glaucoma filtration surgery in a rabbit model.Guoji Yanke Zazhi 2008;8(10).
51.Wunderlich K,Pech M,Eberle AN,Mihatsch M,Flammer J,Meyer P.Expression of connective tissue growth factor(CTGF)mRNA in plaques of human anterior subcapsular cataracts and membranes of posterior capsule opacification.Curr Eye Res 2000;21(2):627-36.
52.Park SK,Kim J,Seomun Y,Choi J,Kim DH,Han IO,et al.Hydrogen peroxide is a novel inducer of connective tissue growth factor.Biochem Biophys Res Commun 2001;284(4):966-71.
53.Bertelmann E,Kojetinsky C.Posterior capsule opacification and anterior capsule opacification.Curr Opin Ophthalmol 2001;12(1):35-40.
54.Marcantonio JM,Vrensen GF.Cell biology of posterior capsular opacification.Eye 1999;13(Pt 3b):484-8.
55.Mootha VV,Tesser R,Quails C.Incidence of and risk factors for residual posterior capsule opacification after cataract surgery.J Cataract Refract Surg 2004;30(11):2354-8.
56.Liu J,Hales AM,Chamberlain CG,McAvoy JW.Induction of cataract-like changes in rat lens epithelial explants by transforming growth factor beta.Invest Ophthalmol Vis Sci 1994;35(2):388-401.
57.Marcantonio JM,Syam PP,Liu CS,Duncan G.Epithelial transdifferentiation and cataract in the human lens.Exp Eye Res 2003;77(3):339-46.
58.Shirai K,Saika S,Okada Y,Oda S,Ohnishi Y Histology and immunohistochemistry of fibrous posterior capsule opacification in an infant.J Cataract Refract Surg 2004;30(2):523-6.
59.惠延年．玻璃体病．眼科学2004；第六版:162-8.
60.Hinton DR,He S,Jin ML,Barron E,Ryan SJ.Novel growth factors involved in the pathogenesis of proliferative vitreoretinopathy.Eye 2002;16(4):422-8.
61.Meyer P,Wunderlich K,Kain HL,Prunte C,Flammer J.Human connective tissue growth factor mRNA expression of epiretinal and subretinal fibrovascular membranes:a report of three cases.Ophthalmologica 2002;216(4):284-91.
62.Kuiper EJ,de Smet MD,van Meurs JC,Tan HS,Tanck MW,Oliver N,et al.Association of connective tissue growth factor with fibrosis in vitreoretinal disorders in the human eye.Arch Ophthalmol 2006;124(10):1457-62.
63.Abu El-Asrar AM,Van den Steen PE,Al-Amro SA,Missotten L,Opdenakker G,Geboes K.Expression of angiogenic and fibrogenic factors in proliferative vitreoretinal disorders.Int Ophthalmol 2007;27(1):11-22.
64.Cui JZ,Chiu A,Maberley D,Ma P,Samad A,Matsubara JA.Stage specificity of novel growth factor expression during development of proliferative vitreoretinopathy.Eye 2007;21(2):200-8.
65.Kita T,Hata Y,Kano K,Miura M,Nakao S,Noda Y,et al.Transforming growth factor-beta2 and connective tissue growth factor in proliferative vitreoretinal diseases:possible involvement of hyalocytes and therapeutic potential of Rho kinase inhibitor.Diabetes 2007;56(1):231-8.
66.Kita T,Hata Y,Miura M,Kawahara S,Nakao S,Ishibashi T.Functional characteristics of connective tissue growth factor on vitreoretinal cells.Diabetes 2007; 56(5):1421-8.
67.Guo Cm,Hui YN,Wang YS,Yan F.The correlation among connective tissue growth factor,tran sform ing growth factor-B receptor,and extracellular matr ix in human prol iferativemembranes of prol iferative v itreoretinopathy.Chin J Ocul Fundus Dis 2006;22(3):192-5.
68.Malone JI,Morrison AD,Pavan PR,Cuthbertson DD.Prevalence and significance of retinopathy in subjects with type 1 diabetes of less than 5 years' duration screened for the diabetes control and complications trial.Diabetes Care 2001;24(3):522-6.
69.Wunderlich K,Senn BC,Todesco L,Flammer J,Meyer P.Regulation of connective tissue growth factor gene expression in retinal vascular endothelial cells by angiogenic growth factors.Graefes Arch Clin Exp Ophthalmol 2000;238(11):910-5.
70.Hinton DR,Spee C,He S,Weitz S,Usinger W,LaBree L,et al.Accumulation of NH2-terminal fragment of connective tissue growth factor in the vitreous of patients with proliferative diabetic retinopathy.Diabetes Care 2004;27(3):758-64.
71.Kuiper EJ,Van Nieuwenhoven FA,de Smet MD,van Meurs JC,Tanck MW,Oliver N,et al.The angio-fibrotic switch of VEGF and CTGF in proliferative diabetic retinopathy.PLoS ONE 2008;3(7):e2675.
72.Kuiper EJ,Witmer AN,Klaassen I,Oliver N,Goldschmeding R,Schlingemann RO.Differential expression of connective tissue growth factor in microglia and pericytes in the human diabetic retina.Br J Ophthalmol 2004;88(8):1082-7.
73.Matsuda S,Gomi F,Katayama T,Koyama Y,Tohyama M,Tano Y.Induction of connective tissue growth factor in retinal pigment epithelium cells by oxidative stress.Jpn J Ophthalmol 2006;50(3):229-34.
74.Hughes JM,Kuiper EJ,Klaassen I,Canning P,Stitt AW,Van Bezu J,et al.Advanced glycation end products cause increased CCN family and extracellular matrix gene expression in the diabetic rodent retina.Diabetologia 2007;50(5):1089-98.
75.He S,Jin ML,Worpel V,Hinton DR.A role for connective tissue growth factor in the pathogenesis of choroidal neovascularization.Arch Ophthalmol 2003;121(9):1283-8.