猪SFRP4基因的表达规律及SP600125对前体脂肪细胞分化的影响
摘要
猪是体脂含量较高的重要经济动物，也是研究体脂沉积的重要模式动物，对猪脂肪细胞中SFRP4表达规律的研究可为猪分子育种以及人类肥胖相关疾病的治疗提供理论基础。然而到目前为止猪SFRP4基因在脂肪组织以及脂肪细胞分化过程中的表达规律还未见相关报道。
Wnt信号转导包括受体卷曲蛋白家族，其包括一个胞外半胱氨酸富集区域（CRD），7个跨膜区域，和一段短胞质尾区，而分泌型卷曲相关蛋白家族成员作为Wnt信号通路可溶解的调控子，调控Wnt信号通路的信号转导。SFRP4作为SFRPs家族成员之一，与其他成员具有相似的功能和结构，而SFRP4对脂肪细胞分化的影响却未见报道。
本研究通过高通量测序（Solexa）技术、实时定量PCR（qRT-PCR）对瘦肉型和脂肪型猪不同生长阶段脂肪组织中SFRP4表达规律进行研究；用western免疫印迹及qRT-PCR技术对脂肪细胞分化过程中SFRP4蛋白表达和mRNA表达进行检测。用JNK信号通路特异性抑制剂SP600125处理猪原代前体脂肪细胞，研究抑制JNK信号通路对猪前体脂肪分化以及SFRP4mRNA和蛋白表达的影响。
主要研究结论如下：
SFRP4在脂肪型猪脂肪组织表达量显著高于瘦肉型猪(P<0.01)；猪不同组织mRNA表达水平检测结果发现，SFRP4广泛表达于各个组织，并高表达于脂肪组织；前体脂肪细胞向成熟脂肪细胞分化过程中SFRP4表达量逐渐升高。
SP600125促进了前体脂肪细胞分化，引起了PPARγ、FABP4、ATGL、Perilipin的显著升高(P<0.01)，而SFRP4的表达却被显著抑制。本研究为调控脂肪细胞分化关键基因的筛选提供新的理论参考。
The porcine is important body fat deposition animal model,and the research on SFRP4expression pattern for pig can provide a theoretical basis for human obesity related diseases a.However there is no reports on pig SFRP4expression patten on porcine.
Wnt signal transduction includes Frizzled related protein family, which includes anextracellular cysteine rich region (CRD),7transmembrane regions, and a short cytoplasmictail. Secreted frizzled related protein family members are part of the Wnt signaling pathwaythat regulat Wnt signaling pathway signal transduction.SFRP4is one of the SFRPs familymembers.
Secreted frizzled-related protein4(SFRP4) is a regulator of Wnt signaling pathway. Theexpression of SFRP4in adipose tissue different growth period in fatty type and lean type pigswere explored by high-throughout sequencing (Solexa) and real-time quantity PCR(qRT-PCR); And its mRNA and protein expression profile during adipogenesis was analysizedby qRT-PCR and Western blot respectively. By using SP600125, a specific inhibitor of JNKsignaling, to treat primarey cultured porcine adiocytes, the effect of JNK signaling inhibitionon differentiation of preadipocyte and the expression of SFRP4were explored. The resultsshowed that expression level of SFRP4was higher in fat tissues of obese-type than that oflean-type. Expression level of SFRP4in the porcine fat tissue was influenced by ages, andshowed a higher expression in fat, but lower in other tissues. SP600125promoteddifferentiation of adiocytes and induced expression of PPARγ, FABP4, ATGL, Perilipinsignificantly, but inhibited expression of SFRP4.This research provides a new reference forscreen the key genes in adipocyte differentiation.
The main conclusions are as follows:
The expression level of SFRP4on fat pig adipose tissue was significantly higher thanthose of lean type pigs (P <0.01); different tissue testing results showed that SFRP4widelyexpressed in various tissues, but highly expressed in adipose tissue; When preasipocytedifferente into mature adipocyte,SFRP4mRNA and protein expression levels were increasedgradually.
SP600125promoted preadipocyte differente into mature adiocytes and inducedexpression of PPARγ, FABP4, ATGL, Perilipin increased significantly, but inhibited expression of SFRP4.This research provides a new reference for screen the key genes inadipocyte differentiation
Wnt信号转导包括受体卷曲蛋白家族，其包括一个胞外半胱氨酸富集区域（CRD），7个跨膜区域，和一段短胞质尾区，而分泌型卷曲相关蛋白家族成员作为Wnt信号通路可溶解的调控子，调控Wnt信号通路的信号转导。SFRP4作为SFRPs家族成员之一，与其他成员具有相似的功能和结构，而SFRP4对脂肪细胞分化的影响却未见报道。
本研究通过高通量测序（Solexa）技术、实时定量PCR（qRT-PCR）对瘦肉型和脂肪型猪不同生长阶段脂肪组织中SFRP4表达规律进行研究；用western免疫印迹及qRT-PCR技术对脂肪细胞分化过程中SFRP4蛋白表达和mRNA表达进行检测。用JNK信号通路特异性抑制剂SP600125处理猪原代前体脂肪细胞，研究抑制JNK信号通路对猪前体脂肪分化以及SFRP4mRNA和蛋白表达的影响。
主要研究结论如下：
SFRP4在脂肪型猪脂肪组织表达量显著高于瘦肉型猪(P<0.01)；猪不同组织mRNA表达水平检测结果发现，SFRP4广泛表达于各个组织，并高表达于脂肪组织；前体脂肪细胞向成熟脂肪细胞分化过程中SFRP4表达量逐渐升高。
SP600125促进了前体脂肪细胞分化，引起了PPARγ、FABP4、ATGL、Perilipin的显著升高(P<0.01)，而SFRP4的表达却被显著抑制。本研究为调控脂肪细胞分化关键基因的筛选提供新的理论参考。
The porcine is important body fat deposition animal model,and the research on SFRP4expression pattern for pig can provide a theoretical basis for human obesity related diseases a.However there is no reports on pig SFRP4expression patten on porcine.
Wnt signal transduction includes Frizzled related protein family, which includes anextracellular cysteine rich region (CRD),7transmembrane regions, and a short cytoplasmictail. Secreted frizzled related protein family members are part of the Wnt signaling pathwaythat regulat Wnt signaling pathway signal transduction.SFRP4is one of the SFRPs familymembers.
Secreted frizzled-related protein4(SFRP4) is a regulator of Wnt signaling pathway. Theexpression of SFRP4in adipose tissue different growth period in fatty type and lean type pigswere explored by high-throughout sequencing (Solexa) and real-time quantity PCR(qRT-PCR); And its mRNA and protein expression profile during adipogenesis was analysizedby qRT-PCR and Western blot respectively. By using SP600125, a specific inhibitor of JNKsignaling, to treat primarey cultured porcine adiocytes, the effect of JNK signaling inhibitionon differentiation of preadipocyte and the expression of SFRP4were explored. The resultsshowed that expression level of SFRP4was higher in fat tissues of obese-type than that oflean-type. Expression level of SFRP4in the porcine fat tissue was influenced by ages, andshowed a higher expression in fat, but lower in other tissues. SP600125promoteddifferentiation of adiocytes and induced expression of PPARγ, FABP4, ATGL, Perilipinsignificantly, but inhibited expression of SFRP4.This research provides a new reference forscreen the key genes in adipocyte differentiation.
The main conclusions are as follows:
The expression level of SFRP4on fat pig adipose tissue was significantly higher thanthose of lean type pigs (P <0.01); different tissue testing results showed that SFRP4widelyexpressed in various tissues, but highly expressed in adipose tissue; When preasipocytedifferente into mature adipocyte,SFRP4mRNA and protein expression levels were increasedgradually.
SP600125promoted preadipocyte differente into mature adiocytes and inducedexpression of PPARγ, FABP4, ATGL, Perilipin increased significantly, but inhibited expression of SFRP4.This research provides a new reference for screen the key genes inadipocyte differentiation
引文
高晓娟,吉红,常志光等.2011. PGC-1和SREBP-1c在猪脂肪细胞分化过程中的相互作用.中国生物化学与分子生物.27:533-539
李新建,杨浩,程佳等.2011.猪TCTP基因的表达规律及其对脂肪细胞分化的影响.中国生物化学与分子生物学报27:444-451
屈长青,张国华,陈粉粉等.2005.猪前体脂肪细胞的原代培养.农业生物技术学报.13:649-653
杨公社,张浩卫,白亮,等.2008.猪—研究肥胖和糖尿病的理想模式动物.自然科学进展.18:481487.
Abu-Jawdeh G, Comella N, Tomita Y, et al.1999. Differential expression of frpHE: a novel human stromalprotein of the secreted frizzled gene family, during the endometrial cycle and malignancy[J]. LabInvest.79:439-47.
Ajit Muley, Syamantak Majumder, Gopi Krishna Kolluru, et al.2010.Secreted Frizzled-Related Protein4:An Angiogenesis Inhibitor[J].The American Journal of Pathology.176:1505–1516
Anna Bafico, Arnona Gazit, Tata Pramila, et al.1999.Interaction of Frizzled Related Protein (FRP) withWnt Ligands and the Frizzled Receptor Suggests Alternative Mechanisms for FRP Inhibition of WntSignaling [J]. The Journal of Biological Chemistry.274:16180-16187
Barak Y, Nelson MC, Ong ES,et al.1999.PPAR gamma is required for placental,cardiac and adipose tissuedevelopment.Mol Cell.4:585-595
Bennett CN, Ross SE, Longo KA, et al.2002.Regulation of Wnt signaling during adipogenesis [J].BiolChem.277:30998-31004.
Biao He, Amie Y. Lee, Sina Dadfarmay, et al.2005. Secreted Frizzled-Related Protein4Is Silenced byHypermethylation and Induces Apoptosis in β-Catenin Deficient Human Mesothelioma[J]. Cells.65(3):743-748
Bodine PV, Komm BS.2006. Wnt signaling and osteoblastogenesis. Rev Endocr Metab Disord7:33–39
Bodine PVN, Zhao W, Kharode YP, et al.2003.The Wnt Antagonist Secreted Frizzled-Related Protein-1Isa Negative Regulator of Trabecular Bone Formation in Adult Mice [J]. MolecularEndocrinology.18:1222–1237
Brendan D Stamper, Sarah S Park, Richard P Beyer,et al.2011.Differential Expression of ExtracellularMatrix-Mediated Pathways in Single-Suture Craniosynostosis [J]. PLoS One.6: e26557
Bu XM, Zhao CH, Zhang N, et al.2008.Hypermethylation and aberrant expression of secretedfrizzled-related protein genes in pancreatic cancer. World J Gastroenterol.14:3421-3424.
Campfield LA, Smith FJ, Burn P.1996.The OB protein–(leptin) pathway—a link between adipose tissuemass and central neural networks. Horm.Metab Res.28:619–632
Chen YR，Wang X，Templeton D，et a1.1996.The role of e-Jun N—terminal kinase(JNK)in apoptosisinduced by ultraviolet C and gamma radiation．Duration of JNK activation may determine cell deathand proliferation．J Biol Chem.271:31929—31936．
Cho HY, Choi HJ, Sun HJ, et al.2010.Transgenic mice overexpressing secreted frizzled-related proteins(sFRP)4under the control of serum amyloid P promoter exhibit low bone mass but did not result indisturbed phosphate homeostasis[J]. Bone.47(2):263–271
Choi YW, Hong S, Jin Q,et al.2009. Histone methylation regulator PTIP is required for PPARg and C/EBPexpression and adipogenesis. Cell Metab.10:27-39.
Christodoulides C, Lagathu C, Sethi JK et al..2009.Adipogenesis and WNT signalling. Trends Endocrinol.Metab.20:16-24.
Christopher L, Hall&Evan T, Keller.2006.The role of Wnts in bone metastases [J]. Cancer Metastasis Rev.25:551–558
Constantinou T, Baumann F, Lacher MD, et al.2008.SFRP-4abrogates Wnt-3a-induced beta-catenin andAkt/PKB signaling and reverses a Wnt-3a-imposed inhibition of in vitro mammary differentiation.[J].J Mol Signal.3:10–23
Cousin W, Fontaine C, Dani C and Peraldi P.2007.Hedgehog and adipogenesis: fat and fiction. Biochimie.89:1447-1453.
Daniel Romaker, Michael Puetz, Sven Teschner, et al.2009.Increased Expression of SecretedFrizzled-Related Protein4in Polycystic Kidneys [J]. J Am Soc Nephrol.20:48–56
Danuta Wawrzak, Mourad Me′tioui, Erik Willems, et al.2007.Wnt3a binds to several sFRPs in thenanomolar range [J]. Biochemical and Biophysical Research Communications.357:1119–1123
Darimont C, Zbinden C, Avanti O et al.2007.Reconstitution of telomerase activity combined with HPV-E7.expression allow human preadipocytes to preserve their differentiation capacity afterimmortalization.Cell Death Diff.10:1025–1031.
Drake J, Shearwood AM, White J et al.2009. Expression of secreted frizzled-related protein4(SFRP4) inprimary serous ovarian tumours [J].Eur J Gynaecol Oncol.30:133-141
Drake JM, Friis RR, Dharmarajan AM, et al.2003.The role of sFRP4, a secreted frizzled-related protein, inovulation [J]. Apoptosis.8:389–397
E, Zhan F, Walker R, et al.2003.The role of the Wnt signaling antagonist DKK1in the development ofosteolytic lesions in multiple myeloma. N Engl J Med.349:2483–94.
Easwaran H, Neste LV, Cope L, et al.2010.Aberrant Silencing of Cancer Related Genes by CpGHypermethylation Occurs Independently of Their Spatial Organization in the Nucleus [J]. Cancer Res.70:8015–8024
Etheridge SL, Spencer GJ, Heath DJ, et al.2004.Expression profiling and functional analysis of wntsignaling mechanism in mesencymal stem cells. Stem Cells.22:849–60.
Faust IM, Johnson PR, Stern JS&Hirsch J.1978. Diet-induced adipocyte number increase in adult rats: anew model of obesity. Am J Physiol.235: E279–E286.
Faust IM, Miller WH, Sclafanni A, et al.1984.Diet-dependent hypeplastic growth of adipose tissue inhypothalamic obese rats. Am J Physiol.247: R1038–R1046.
Feng Han Q, Zhao W, Bentel J, et al.2006. Expression of sFRP-4and beta-catenin in human colorectalcarcinoma. Cancer Lett.231:129-37.
Fox S, Dharmarajan A.2006.WNT signaling in malignant mesothelioma [J]. Front Biosci.11:2106–2112
Francis J, Kristjan U, Sheri N, et al.2012.Loss of Secreted Frizzled-Related Protein4Correlates with anAggressive Phenotype and Predicts Poor Outcome in Ovarian Cancer Patients [J]. PLoS One.7:e31885
Fu L, Tang T, Miao Y, et al.2008.Stimulation of osteogenic differentiation and inhibition of adipogenicdifferentiation in bone marrow stromal cells by alendronate via ERK and JNK activation [J].Bone.43:40-47
Fujita M, Ogawa S, Fukuoka H, et al.2002.Differential expression of secreted frizzled-related protein4indecidual cells during pregnancy[J]. J Mol Endocrinol.28(3):213-23.
Green H&Kehinde O.1975.An established preadipose cell and its differentiation in culture. II. Factorsaffecting the adipose conversion. Cell.5:19-27.
Green H&Kehinde O.1979.Formation of normally differentiated subcutaneous fat pads from anestablished preadipose cell line. J Cell Physiol.101:169-171.
Green H&Kehinde O.1976.Spontaneous heritable changes leading to increased adipose conversion in3T3cells. Cell.7:105-113.
Green H&Meuth M.1974. An established preadipose cell and its differentiation in culture. Cell.3:127-133.
Grimaldi B, Bellet MM, Katada S, et al.2010.PER2controls lipid metabolism by direct regulation ofPPARg. Cell Metab.12:509-520.
Gulsan Ara Sathi, Miho Inoue, Hidemitsu Harada,et al.2009.Secreted frizzled related protein (sFRP)-2inhibits bone formation and promotes cell proliferation in ameloblastoma[J]. Oral Oncology.45:856–860
Guo K, Wolf V, Dharmarajan AM, et al.1998.Apoptosis-associated gene expression in the corpus luteumof the rat. Biol Reprod.58:739–46.
Hirosumi J, Tuncman G, Chang L, et al.2002.A central role for JNK in obesity and insulinresistance.Nature.420:333-336．
Hotamisligil, G. S.2010. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease.Cell.140,900-917.
Hrzenjak A, Tippl M, Kremser ML, et al.2004.Inverse correlation of secreted frizzled-related protein4andbeta-catenin expression in endometrial stromal sarcomas. J Pathol.204:19-27.
Hsieh M, Mulders SM, Friis RR.2003.Expression and localization of secreted frizzled-related protein-4inthe rodent ovary: evidence for selective up-regulation in luteinized granulosa cells [J].Endocrinology.144(10):4597–4606
Huang D, Yu B, Deng Y, et al.2010. SFRP4was overexpressed in colorectal carcinoma [J].J Cancer ResClin Oncol.136(3):395–401
Hwa Young Cho, Hyung Jin Choi, Hyun Jin Sun, et al.2010.Transgenic mice overexpressing secretedfrizzled-related proteins (sFRP)4under the control of serum amyloid P promoter exhibit low bonemass but did not result in disturbed phosphate homeostasis[J].Bone.47:263–271
Jing E, Gesta S.and Kahn CR.2007.SIRT2regulates adipocyte differentiation through FoxO1acetylation/deacetylation. Cell Metab.6:105-114.
Jiyun Ahn, Hyunjung Lee, Suna Kim, et al.2010.Curcumin-induced suppression of adipogenicdifferentiation is accompanied by activation of Wnt/b-catenin signaling [J]. Am J Physiol CellPhysiol.298: C1510–C1516
Julie Bayle, Jennifer Fitch, Kimberly Jacobsen, et al.2008.Increased Expression of Wnt2and SFRP4in TskMouse Skin: Role of Wnt Signaling in Altered Dermal Fibrillin Deposition and Systemic Sclerosis.Journal of Investigative Dermatology.128:871–881.
Kang GH, Lee S, Cho NY,et al.2008.DNA methylation profiles of gastric carcinoma characterized byquantitative DNA methylation analysis. Lab Invest.88:161-170.
Kawai M, Green CB, Lecka-Czernik B, et al.2010.A circadian-regulated gene, Nocturnin, promotesadipogenesis by stimulating PPAR-g nuclear translocation. Proc. Natl. Acad.Sci.107:10508-10513.
Kendra S. Carmon and David S. Loose.2008. Secreted Frizzled-Related Protein4Regulates Two Wnt7aEndometrial Signaling Pathways and Inhibits Proliferation in Cancer Cells[J]. Mol CancerRes.6:1017-1028.
Kendra S. Carmon, David S. Loose.2010. Development of a bioassay for detection of Wnt-bindingaffinities for individual frizzled receptors[J]. Analytical Biochemistry.401:288–294
Kendra SC, David SL.2010. Development of a Bioassay for Detection of Wnt Binding Affinities forIndividual Frizzled Receptors [J].Anal Biochem.401:288-294
Kuczmarski RJ, Flegal KM, Campbell SM, et al.1994. Increasing prevalence of overweight among USadults. The National Health and Nutrition Examination Surveys.JAMA.272:205–211
L. Bányai, L. Patthy.1999.The NTR module: domains of netrins, secreted frizzled related proteins, andtype I procollagen C-proteinase enhancer protein are homologous with tissue inhibitors ofmetalloproteases[J]. Protein Sci.8:1636–1642
L Fu, T Tang, Y Miao, et al.2008. Stimulation of osteogenic differentiation and inhibition of adipogenicdifferentiation in bone marrow stromal cells by alendronate via ERK and JNK activation,Bone.43:40–47.
Langin D, Dicker A, Tavernier G, et al.2005.Adipocyte lipases and defect of lipolysis in human obes ity[J]. Diabe t es.54:3190-3197
Lee AY, He B, You L,et al.2004.Expression of the secreted frizzled-related protein gene family isdownregulated in human mesothelioma.Oncogene.23:6672-6676.
Levresse V，Marek L，Blumberg D. et a1.2002. Regulation of platinum—·compound cytotoxicity by thee-Jun N—-terminal kinase and c-Jun signaling pathway in small-eell lung cancer cells．Mol Pharmacol62:689—697
Liu TH, Raval A, Chen SS, et al.2006.CpG island methylation and expression of the secretedfrizzled-related protein gene family in chronic lymphocytic leukemia. Cancer Res.66:653-8.
Londos C, Brasaemle DL, Schu ltz CJ, et al.1999.On the control of lipolysis in adipocytes. Ann N Y Acad Sc.892:155-168.
Londos C, Sztalryd C, Tansey JT, et a.l.2005. Role of PAT proteins in lipid metabolism.Biochimie.8745~8749.
Lowell B B.1999.PPARgamma: an essential regulator of adipogenesis and modulator of fat cellfunction.Cell,99(3):239-242
Luo X, Hutley LJ, Webster JA,et al.2011.Identification of BAMBI as a Potent Negative Regulator ofAdipogenesis and Modulator of Autocrine/Paracrine Adipogenic Factors. Diabetes.
Lynn E. Heasley and Robert A. Winn.2008. Analysis of Wnt7a-Stimulated JNK Activity and cJunPhosphorylation in Non-Small Cell Lung Cancer Cells[J]. Methods in MolecularBiology.468:187-196,
M Montcouquiol, EB Crenshaw, MW Kelley.2006.NoncanonicalWnt signaling and neural polarity, Annu.Rev. Neurosci.29:363–386.
Mansouri A, Ridgway LD, Korapati AL. et al.2003.Sustained activation of JNK／p38MAPK pathways inresponse to cisplatin leads to Fas ligand induction and cell death in ovarian carcinoma cells．J BiolChem.278：19245-19256．
MD Lacher, A Siegenthaler,RJa¨ger, Xi Yan, et al.2003. Role of DDC-4/sFRP-4, a secretedFrizzled-related protein, at the onset of apoptosis in mammary involution[J]. Cell Death andDifferentiation.10:528–538
Miller WH, Faust IM, Hirsch J.1984. Demonstration of de novo production of adipocytes in adult rats bybiochemical and radioautographic techniques. J Lipid Res.25:336–347.
Minden A, Karin M.1997. Regulation and function of the JNK subgroup of MAP kinases. BiochimBiophys Acta.l333:F85-F104
Moran A, Arikan AA, Mary AA. et al.2008. Prevention of Trauma and Hemorrhagic Shock-Mediated LiverApoptosis by Activation of Stat3α [J]. Int J Clin Exp Med.1:213–247.
Nakanishi R, Akiyama H, Kimura H, et al.2008. Osteoblast-Targeted Expression of Sfrp4in Mice Resultsin LowBone Mass[J]. Journal of Bone and Mineral Research.23:271-277
Nakanishi R, Akiyama H, Kimura H, et al.2008. Osteoblast-targeted expression of SFRP4in mice results inlow bone mass. J Bone Miner Res.23:271–277.
Negrel R. Grimaldi P&Ailhaud G.1978. Establishment of preadipocyte clonal line from epididymal fatpad of ob/ob mouse that responds to insulin and to lipolytic hormones. Proc Natl Acad Sci USA.75:6054–6058.
Nicola G, Simona C, Francesca M, et al.2005. Myeloma cells block RUNX2/CBFA1activity in humanbone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation[J].Blood,.106:2472-2483
Noriyuki Ouchi, Akiko Higuchi, Koji Ohashi, et al.2010.Sfrp5Is an Anti-Inflammatory Adipokine ThatModulates Metabolic Dysfunction in Obesity[J].Science.329:454-457
Oshima T, Abe M, Asano J, et al.2005.Myeloma cells suppress bone formation by secreting soluble Wntinhibitor SFRP-2. Blood.106:3160–3165.
Park JR, Jung JW, Lee YS, et al.2008.The roles of Wnt antagonists Dkk1and SFRP4during adipogenesisof human adipose tissue-derived mesenchymal stem cells [J].Cell Prolif.41:859-874
Peter VN Bodine, Barbara Stauffer, Helga Ponce-de-Leon et al.2009.A small molecule inhibitor of the Wntantagonist secreted frizzled-related protein-1stimulates bone formation [J].BONE.44:1063–1068
Picard F, Kurtev M, Chung, N, et al.2004. Sirt1promotes fat mobilization in white adipocytes byrepressing PPAR-gamma. Nature.429:771-776.
Pinent M, Hackl H, Burkard T R, et al.2008.Differential transcriptional modulat i on of biological processesi n adipocyte tri glyceride lipase and hormone sensitive lipase deficient mice [J]. Genomics.92:26-32
Pospisilik JA, Schramek D, Schnidar H, et al.2010. Drosophila genomewide obesity screen revealsHedgehog as a determinant of brown versus white adipose cell fate. Cell.140:148-160.
Prestwich TC, MacDougald OA.2007.Wnt/[beta]-catenin signaling in adipogenesis and metabolism. Curr.Opin. Cell Biol.19:612-617.
Rattner A, Hsieh JC, Smallwood PM, et al.1997.A family of secreted proteins contains homology to thecysteine-rich ligand-binding domain of frizzled receptors [J].Proc Natl Acad Sci.94:2859-2863
Rattner A, Hsieh JC, Smallwood PM, et al.1997.A family of secreted proteins contains homology to thecysteine-rich ligand-binding domain of frizzled receptors[J]. FEBS.417:385–389
Richard Maganga, Natalie Giles, Katharine Adcroft, et al.2008.Secreted Frizzled related protein-4(sFRP4) promotes epidermal differentiation and apoptosis [J]. Biochemical and Biophysical ResearchCommunications.377:606–611
Rika Nakanishi, Motoyuki Shimizu, Masayuki Mori, et al.2006.Secreted Frizzled-Related Protein4Is aNegative Regulator of Peak BMD in SAMP6Mice[J]. of Bone and Mineral Research.21:1713–1721
Risinger JI, Maxwell GL, Chandramouli GV, et al.2005. Gene expression profiling of microsatelliteunstable and microsatellite stable endometrial cancers indicates distinct pathways of aberrant signaling.Cancer Res.65:5031-5037.
Rodriguez AM, Pisani D, Dechesne CA et al.2005.Transplantation of a multipotent cell population fromhuman adipose tissue induces dystrophin expression in the immunocompetent mdx mouse. J Exp Med.201:1397–1405.
Romaker D, Puetz M, Teschner S, et al.2009. Increased Expression of Secreted Frizzled-Related Protein4in Polycystic Kidneys [J] J Am Soc Nephrol.20:48–56
Rosen ED, Sarraf P, Troy AE, et al.1999.PPAR gamma is required for the differentiation of adipose tissuein viro andin vitro.Mol cell.4:611-617
Roth W, et al.2000.Secreted Frizzled-related proteins inhibit motility and promote growth of humanmalignant glioma cells. Oncogene.19:4210-4220.
Ryden M, Jocken J, van Harmelen V, et al.2007.Comparative studies of the role of hormones ensitivelipase and adipose trigl yceride l i pase in human fat cell lipol ysi s [J]. Am J Physi ol EndocrinolMetab,292: E1847-1855
S Tominaga, T Yamaguchi, S Takahashi, et al.2005. Negative regulation of adipogenesis from humanmesenchymal stem cells by Jun N-terminal kinase, Biochem. Biophys. Res. Commun.326:499–504.
Schumann H, Holtz J, Zerkowski HR et al.2000. Expression of secreted frizzled related proteins3and4inhuman ventricular myocardium correlates with apoptosis related gene expression [J]. Cardiovasc Res.45:720-728
Seema Kumar, Alexey Leontovich, Michael J Coenen, et al.2005.Gene Expression Profiling of OrbitalAdipose Tissue from Patients with Graves’ Ophthalmopathy: A Potential Role for SecretedFrizzled-Related Protein-1in Orbital Adipogenesis [J]. The Journal of Clinical Endocrinology&Metabolism.90:4730–4735
Suzuki H, Watkins DN, Jair KW, et al.2004. Epigenetic inactivation of SFRP genes allows constitutiveWNT signaling in colorectal cancer [J].Nat Genet.36:417-422
Suzuki S, Sembon S, Iwamoto M, et al.2008.Identification of genes downregulated during differentiation ofporcine mesenteric [J]. ANIM SCI.86:3367-3376.
Thecla Constantinou, Fabrizio Baumann, Markus D Lacher,et al.2004.SFRP-4abrogates Wnt-3a-inducedβ-catenin and Akt/PKB; obesity. Cell. Mol. Life Sci.67:1277-1292.
Ting AH, Suzuki H, Cope L, et al.2008.A Requirement for DICER to Maintain Full Promoter CpG IslandHypermethylation in Human Cancer Cells [J]. Cancer Res.68:2570–2575
Tominaga S, Yamaguchi T, Takahashi S, et al.2005.Negative regulation of adipogenesis from humanmesenchymal stem cells by Jun N-terminal kinase [J], Biochem Biophys Res Commun.326:499-504
Tontonoz P, Hu E, Spiegelman BM.1994.Stimulation of adiopgenesis in fibroblasts by PPARgamma2,alipid-activated transcription factor.Cell.79:1147-1156
Toshio M, Tanaka, Hironobu S, et al.2005. Myeloma cells suppress bone formation by secreting a solubleWnt inhibitor, sFRP-2[J].Blood.106:3160-3165
Tuncman G, Hir osumi J, Solinas G, et al.2003.Functi onal in vivo in2teractions bet ween JNK1and JNK2is oforms in obesity and insulin resistance[J]. Proc NatlAcad Sci USA.103:107412-10746.
Turashvili G, Bouchal J, Burkadze G, et al.2003. Wnt signaling pathway in mammary gland developmentand carcinogenesis. Pathobiology.73:213-23.
V Mohsen-Kanson, T Ladoux, A Elabd C. et al.2010. Activin A plays a critical role in proliferation anddifferentiation of human adipose progenitors. Diabetes.59:2513-2521.
Valet P, Tavernier G, Castan-Laurell I et al.2002.Understanding adipose tissue development from transgenicanimal models. J Lipid Res.43:835–860.
Wabitsch M, Brenner RE, Melzner I, et al.2001.Characterization of a human preadipocyte cell strain withhigh capacity for adipose differentiation. Int J Obes Relat Metab Disord.25:8–15.
Wabitsch M, Bruderlein S, Melzner I, et al.2000. Lisa-2, a novel human liposarcoma cell line with a highcapacity for terminal adipose differentiation. Int J Cancer.88:889–894.
Wang S P, Laurin N, Himms Hagen J, e t al.2001.The adipose t is sue phenotype of hormone sensitivelipase deficiency in mice [J]. Obes Res.9:119-128
Wang S, Krinks M, Lin K, et al.1997. Frzb, a Secreted Protein Expressed in the Spemann Organizer, Bindsand Inhibits Wnt-8[J].Cell.88:757-766
Wang YX, Lee CH, Tiep S, et al.2003. Peroxisome-proliferator-activated receptor delta activates fatmetabolism to prevent obesity.cell.113:159-170
White L, Suganthini G, Friis R, et al.2009. Expression of secreted frizzled-related protein4in the primateplacenta[J]. Reprod Biomed Online.18:104–111
Widberg CH, Newell FS, Bachmann A. et al.2009. Fibroblast growth factor receptor1is a key regulator ofearly adipogenic events in human preadipocytes. Am. J. Physiol. Endocrinol.Metab.296:E121-E131.
Yam JWP, Chan KW, Ngan ESW, et al.2005. Genomic structure, alternative splicing and tissue expressionof rFrp/sFRP-4, the rat frizzled related protein gene [J]. Gene.357:55–62
Yeaman,SJ.1990.Hormone-sensitive lipase-a multipurpose enzyme in lipid metabolism[J].BiochimBiophys Acta.1052:128-132
Zamani N. and Brown CW.2010. Emerging roles for the transforming growth factor-beta superfamily inregulating adiposity and energy expenditure. Endocr. Rev.32:387-403.
Zhang Y, Chen FQ, Sun YH et al.2011.Effects of DNMT1silencing on malignant phenotype andmethylated gene expression in cervical cancer cells [J]. J Exp Clin Cancer Res.30:98
Zilberfarb V, Pietri-Rouxel F, Jockers R, et al.1997. Human immortalized brown adipocytes expressfunctional beta3-adrenoceptor coupled to lipolysis. J Cell Sci.110:801–807.
Zizola CF, Frey SK, Jitngarmkusol, S, et al.2010. Cellular retinol-binding protein type I (CRBP-I)regulates adipogenesis. Mol. Cell.Biol.30:3412-3420.
Zou H, Molina JR, Harrington JJ, et al.2010.Aberrant methylation of secreted frizzled-related proteingenes in esophageal adenocarcinoma and Barrett's esophagus. Int J Cancer.116(4):584-91.
Zú iga LA, Shen WJ, Joyce-Shaikh B, et al.2010. IL-17regulates adipogenesis, glucose homeostasis, andobesity. J.Immunol.185:6947-6959.
李新建,杨浩,程佳等.2011.猪TCTP基因的表达规律及其对脂肪细胞分化的影响.中国生物化学与分子生物学报27:444-451
屈长青,张国华,陈粉粉等.2005.猪前体脂肪细胞的原代培养.农业生物技术学报.13:649-653
杨公社,张浩卫,白亮,等.2008.猪—研究肥胖和糖尿病的理想模式动物.自然科学进展.18:481487.
Abu-Jawdeh G, Comella N, Tomita Y, et al.1999. Differential expression of frpHE: a novel human stromalprotein of the secreted frizzled gene family, during the endometrial cycle and malignancy[J]. LabInvest.79:439-47.
Ajit Muley, Syamantak Majumder, Gopi Krishna Kolluru, et al.2010.Secreted Frizzled-Related Protein4:An Angiogenesis Inhibitor[J].The American Journal of Pathology.176:1505–1516
Anna Bafico, Arnona Gazit, Tata Pramila, et al.1999.Interaction of Frizzled Related Protein (FRP) withWnt Ligands and the Frizzled Receptor Suggests Alternative Mechanisms for FRP Inhibition of WntSignaling [J]. The Journal of Biological Chemistry.274:16180-16187
Barak Y, Nelson MC, Ong ES,et al.1999.PPAR gamma is required for placental,cardiac and adipose tissuedevelopment.Mol Cell.4:585-595
Bennett CN, Ross SE, Longo KA, et al.2002.Regulation of Wnt signaling during adipogenesis [J].BiolChem.277:30998-31004.
Biao He, Amie Y. Lee, Sina Dadfarmay, et al.2005. Secreted Frizzled-Related Protein4Is Silenced byHypermethylation and Induces Apoptosis in β-Catenin Deficient Human Mesothelioma[J]. Cells.65(3):743-748
Bodine PV, Komm BS.2006. Wnt signaling and osteoblastogenesis. Rev Endocr Metab Disord7:33–39
Bodine PVN, Zhao W, Kharode YP, et al.2003.The Wnt Antagonist Secreted Frizzled-Related Protein-1Isa Negative Regulator of Trabecular Bone Formation in Adult Mice [J]. MolecularEndocrinology.18:1222–1237
Brendan D Stamper, Sarah S Park, Richard P Beyer,et al.2011.Differential Expression of ExtracellularMatrix-Mediated Pathways in Single-Suture Craniosynostosis [J]. PLoS One.6: e26557
Bu XM, Zhao CH, Zhang N, et al.2008.Hypermethylation and aberrant expression of secretedfrizzled-related protein genes in pancreatic cancer. World J Gastroenterol.14:3421-3424.
Campfield LA, Smith FJ, Burn P.1996.The OB protein–(leptin) pathway—a link between adipose tissuemass and central neural networks. Horm.Metab Res.28:619–632
Chen YR，Wang X，Templeton D，et a1.1996.The role of e-Jun N—terminal kinase(JNK)in apoptosisinduced by ultraviolet C and gamma radiation．Duration of JNK activation may determine cell deathand proliferation．J Biol Chem.271:31929—31936．
Cho HY, Choi HJ, Sun HJ, et al.2010.Transgenic mice overexpressing secreted frizzled-related proteins(sFRP)4under the control of serum amyloid P promoter exhibit low bone mass but did not result indisturbed phosphate homeostasis[J]. Bone.47(2):263–271
Choi YW, Hong S, Jin Q,et al.2009. Histone methylation regulator PTIP is required for PPARg and C/EBPexpression and adipogenesis. Cell Metab.10:27-39.
Christodoulides C, Lagathu C, Sethi JK et al..2009.Adipogenesis and WNT signalling. Trends Endocrinol.Metab.20:16-24.
Christopher L, Hall&Evan T, Keller.2006.The role of Wnts in bone metastases [J]. Cancer Metastasis Rev.25:551–558
Constantinou T, Baumann F, Lacher MD, et al.2008.SFRP-4abrogates Wnt-3a-induced beta-catenin andAkt/PKB signaling and reverses a Wnt-3a-imposed inhibition of in vitro mammary differentiation.[J].J Mol Signal.3:10–23
Cousin W, Fontaine C, Dani C and Peraldi P.2007.Hedgehog and adipogenesis: fat and fiction. Biochimie.89:1447-1453.
Daniel Romaker, Michael Puetz, Sven Teschner, et al.2009.Increased Expression of SecretedFrizzled-Related Protein4in Polycystic Kidneys [J]. J Am Soc Nephrol.20:48–56
Danuta Wawrzak, Mourad Me′tioui, Erik Willems, et al.2007.Wnt3a binds to several sFRPs in thenanomolar range [J]. Biochemical and Biophysical Research Communications.357:1119–1123
Darimont C, Zbinden C, Avanti O et al.2007.Reconstitution of telomerase activity combined with HPV-E7.expression allow human preadipocytes to preserve their differentiation capacity afterimmortalization.Cell Death Diff.10:1025–1031.
Drake J, Shearwood AM, White J et al.2009. Expression of secreted frizzled-related protein4(SFRP4) inprimary serous ovarian tumours [J].Eur J Gynaecol Oncol.30:133-141
Drake JM, Friis RR, Dharmarajan AM, et al.2003.The role of sFRP4, a secreted frizzled-related protein, inovulation [J]. Apoptosis.8:389–397
E, Zhan F, Walker R, et al.2003.The role of the Wnt signaling antagonist DKK1in the development ofosteolytic lesions in multiple myeloma. N Engl J Med.349:2483–94.
Easwaran H, Neste LV, Cope L, et al.2010.Aberrant Silencing of Cancer Related Genes by CpGHypermethylation Occurs Independently of Their Spatial Organization in the Nucleus [J]. Cancer Res.70:8015–8024
Etheridge SL, Spencer GJ, Heath DJ, et al.2004.Expression profiling and functional analysis of wntsignaling mechanism in mesencymal stem cells. Stem Cells.22:849–60.
Faust IM, Johnson PR, Stern JS&Hirsch J.1978. Diet-induced adipocyte number increase in adult rats: anew model of obesity. Am J Physiol.235: E279–E286.
Faust IM, Miller WH, Sclafanni A, et al.1984.Diet-dependent hypeplastic growth of adipose tissue inhypothalamic obese rats. Am J Physiol.247: R1038–R1046.
Feng Han Q, Zhao W, Bentel J, et al.2006. Expression of sFRP-4and beta-catenin in human colorectalcarcinoma. Cancer Lett.231:129-37.
Fox S, Dharmarajan A.2006.WNT signaling in malignant mesothelioma [J]. Front Biosci.11:2106–2112
Francis J, Kristjan U, Sheri N, et al.2012.Loss of Secreted Frizzled-Related Protein4Correlates with anAggressive Phenotype and Predicts Poor Outcome in Ovarian Cancer Patients [J]. PLoS One.7:e31885
Fu L, Tang T, Miao Y, et al.2008.Stimulation of osteogenic differentiation and inhibition of adipogenicdifferentiation in bone marrow stromal cells by alendronate via ERK and JNK activation [J].Bone.43:40-47
Fujita M, Ogawa S, Fukuoka H, et al.2002.Differential expression of secreted frizzled-related protein4indecidual cells during pregnancy[J]. J Mol Endocrinol.28(3):213-23.
Green H&Kehinde O.1975.An established preadipose cell and its differentiation in culture. II. Factorsaffecting the adipose conversion. Cell.5:19-27.
Green H&Kehinde O.1979.Formation of normally differentiated subcutaneous fat pads from anestablished preadipose cell line. J Cell Physiol.101:169-171.
Green H&Kehinde O.1976.Spontaneous heritable changes leading to increased adipose conversion in3T3cells. Cell.7:105-113.
Green H&Meuth M.1974. An established preadipose cell and its differentiation in culture. Cell.3:127-133.
Grimaldi B, Bellet MM, Katada S, et al.2010.PER2controls lipid metabolism by direct regulation ofPPARg. Cell Metab.12:509-520.
Gulsan Ara Sathi, Miho Inoue, Hidemitsu Harada,et al.2009.Secreted frizzled related protein (sFRP)-2inhibits bone formation and promotes cell proliferation in ameloblastoma[J]. Oral Oncology.45:856–860
Guo K, Wolf V, Dharmarajan AM, et al.1998.Apoptosis-associated gene expression in the corpus luteumof the rat. Biol Reprod.58:739–46.
Hirosumi J, Tuncman G, Chang L, et al.2002.A central role for JNK in obesity and insulinresistance.Nature.420:333-336．
Hotamisligil, G. S.2010. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease.Cell.140,900-917.
Hrzenjak A, Tippl M, Kremser ML, et al.2004.Inverse correlation of secreted frizzled-related protein4andbeta-catenin expression in endometrial stromal sarcomas. J Pathol.204:19-27.
Hsieh M, Mulders SM, Friis RR.2003.Expression and localization of secreted frizzled-related protein-4inthe rodent ovary: evidence for selective up-regulation in luteinized granulosa cells [J].Endocrinology.144(10):4597–4606
Huang D, Yu B, Deng Y, et al.2010. SFRP4was overexpressed in colorectal carcinoma [J].J Cancer ResClin Oncol.136(3):395–401
Hwa Young Cho, Hyung Jin Choi, Hyun Jin Sun, et al.2010.Transgenic mice overexpressing secretedfrizzled-related proteins (sFRP)4under the control of serum amyloid P promoter exhibit low bonemass but did not result in disturbed phosphate homeostasis[J].Bone.47:263–271
Jing E, Gesta S.and Kahn CR.2007.SIRT2regulates adipocyte differentiation through FoxO1acetylation/deacetylation. Cell Metab.6:105-114.
Jiyun Ahn, Hyunjung Lee, Suna Kim, et al.2010.Curcumin-induced suppression of adipogenicdifferentiation is accompanied by activation of Wnt/b-catenin signaling [J]. Am J Physiol CellPhysiol.298: C1510–C1516
Julie Bayle, Jennifer Fitch, Kimberly Jacobsen, et al.2008.Increased Expression of Wnt2and SFRP4in TskMouse Skin: Role of Wnt Signaling in Altered Dermal Fibrillin Deposition and Systemic Sclerosis.Journal of Investigative Dermatology.128:871–881.
Kang GH, Lee S, Cho NY,et al.2008.DNA methylation profiles of gastric carcinoma characterized byquantitative DNA methylation analysis. Lab Invest.88:161-170.
Kawai M, Green CB, Lecka-Czernik B, et al.2010.A circadian-regulated gene, Nocturnin, promotesadipogenesis by stimulating PPAR-g nuclear translocation. Proc. Natl. Acad.Sci.107:10508-10513.
Kendra S. Carmon and David S. Loose.2008. Secreted Frizzled-Related Protein4Regulates Two Wnt7aEndometrial Signaling Pathways and Inhibits Proliferation in Cancer Cells[J]. Mol CancerRes.6:1017-1028.
Kendra S. Carmon, David S. Loose.2010. Development of a bioassay for detection of Wnt-bindingaffinities for individual frizzled receptors[J]. Analytical Biochemistry.401:288–294
Kendra SC, David SL.2010. Development of a Bioassay for Detection of Wnt Binding Affinities forIndividual Frizzled Receptors [J].Anal Biochem.401:288-294
Kuczmarski RJ, Flegal KM, Campbell SM, et al.1994. Increasing prevalence of overweight among USadults. The National Health and Nutrition Examination Surveys.JAMA.272:205–211
L. Bányai, L. Patthy.1999.The NTR module: domains of netrins, secreted frizzled related proteins, andtype I procollagen C-proteinase enhancer protein are homologous with tissue inhibitors ofmetalloproteases[J]. Protein Sci.8:1636–1642
L Fu, T Tang, Y Miao, et al.2008. Stimulation of osteogenic differentiation and inhibition of adipogenicdifferentiation in bone marrow stromal cells by alendronate via ERK and JNK activation,Bone.43:40–47.
Langin D, Dicker A, Tavernier G, et al.2005.Adipocyte lipases and defect of lipolysis in human obes ity[J]. Diabe t es.54:3190-3197
Lee AY, He B, You L,et al.2004.Expression of the secreted frizzled-related protein gene family isdownregulated in human mesothelioma.Oncogene.23:6672-6676.
Levresse V，Marek L，Blumberg D. et a1.2002. Regulation of platinum—·compound cytotoxicity by thee-Jun N—-terminal kinase and c-Jun signaling pathway in small-eell lung cancer cells．Mol Pharmacol62:689—697
Liu TH, Raval A, Chen SS, et al.2006.CpG island methylation and expression of the secretedfrizzled-related protein gene family in chronic lymphocytic leukemia. Cancer Res.66:653-8.
Londos C, Brasaemle DL, Schu ltz CJ, et al.1999.On the control of lipolysis in adipocytes. Ann N Y Acad Sc.892:155-168.
Londos C, Sztalryd C, Tansey JT, et a.l.2005. Role of PAT proteins in lipid metabolism.Biochimie.8745~8749.
Lowell B B.1999.PPARgamma: an essential regulator of adipogenesis and modulator of fat cellfunction.Cell,99(3):239-242
Luo X, Hutley LJ, Webster JA,et al.2011.Identification of BAMBI as a Potent Negative Regulator ofAdipogenesis and Modulator of Autocrine/Paracrine Adipogenic Factors. Diabetes.
Lynn E. Heasley and Robert A. Winn.2008. Analysis of Wnt7a-Stimulated JNK Activity and cJunPhosphorylation in Non-Small Cell Lung Cancer Cells[J]. Methods in MolecularBiology.468:187-196,
M Montcouquiol, EB Crenshaw, MW Kelley.2006.NoncanonicalWnt signaling and neural polarity, Annu.Rev. Neurosci.29:363–386.
Mansouri A, Ridgway LD, Korapati AL. et al.2003.Sustained activation of JNK／p38MAPK pathways inresponse to cisplatin leads to Fas ligand induction and cell death in ovarian carcinoma cells．J BiolChem.278：19245-19256．
MD Lacher, A Siegenthaler,RJa¨ger, Xi Yan, et al.2003. Role of DDC-4/sFRP-4, a secretedFrizzled-related protein, at the onset of apoptosis in mammary involution[J]. Cell Death andDifferentiation.10:528–538
Miller WH, Faust IM, Hirsch J.1984. Demonstration of de novo production of adipocytes in adult rats bybiochemical and radioautographic techniques. J Lipid Res.25:336–347.
Minden A, Karin M.1997. Regulation and function of the JNK subgroup of MAP kinases. BiochimBiophys Acta.l333:F85-F104
Moran A, Arikan AA, Mary AA. et al.2008. Prevention of Trauma and Hemorrhagic Shock-Mediated LiverApoptosis by Activation of Stat3α [J]. Int J Clin Exp Med.1:213–247.
Nakanishi R, Akiyama H, Kimura H, et al.2008. Osteoblast-Targeted Expression of Sfrp4in Mice Resultsin LowBone Mass[J]. Journal of Bone and Mineral Research.23:271-277
Nakanishi R, Akiyama H, Kimura H, et al.2008. Osteoblast-targeted expression of SFRP4in mice results inlow bone mass. J Bone Miner Res.23:271–277.
Negrel R. Grimaldi P&Ailhaud G.1978. Establishment of preadipocyte clonal line from epididymal fatpad of ob/ob mouse that responds to insulin and to lipolytic hormones. Proc Natl Acad Sci USA.75:6054–6058.
Nicola G, Simona C, Francesca M, et al.2005. Myeloma cells block RUNX2/CBFA1activity in humanbone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation[J].Blood,.106:2472-2483
Noriyuki Ouchi, Akiko Higuchi, Koji Ohashi, et al.2010.Sfrp5Is an Anti-Inflammatory Adipokine ThatModulates Metabolic Dysfunction in Obesity[J].Science.329:454-457
Oshima T, Abe M, Asano J, et al.2005.Myeloma cells suppress bone formation by secreting soluble Wntinhibitor SFRP-2. Blood.106:3160–3165.
Park JR, Jung JW, Lee YS, et al.2008.The roles of Wnt antagonists Dkk1and SFRP4during adipogenesisof human adipose tissue-derived mesenchymal stem cells [J].Cell Prolif.41:859-874
Peter VN Bodine, Barbara Stauffer, Helga Ponce-de-Leon et al.2009.A small molecule inhibitor of the Wntantagonist secreted frizzled-related protein-1stimulates bone formation [J].BONE.44:1063–1068
Picard F, Kurtev M, Chung, N, et al.2004. Sirt1promotes fat mobilization in white adipocytes byrepressing PPAR-gamma. Nature.429:771-776.
Pinent M, Hackl H, Burkard T R, et al.2008.Differential transcriptional modulat i on of biological processesi n adipocyte tri glyceride lipase and hormone sensitive lipase deficient mice [J]. Genomics.92:26-32
Pospisilik JA, Schramek D, Schnidar H, et al.2010. Drosophila genomewide obesity screen revealsHedgehog as a determinant of brown versus white adipose cell fate. Cell.140:148-160.
Prestwich TC, MacDougald OA.2007.Wnt/[beta]-catenin signaling in adipogenesis and metabolism. Curr.Opin. Cell Biol.19:612-617.
Rattner A, Hsieh JC, Smallwood PM, et al.1997.A family of secreted proteins contains homology to thecysteine-rich ligand-binding domain of frizzled receptors [J].Proc Natl Acad Sci.94:2859-2863
Rattner A, Hsieh JC, Smallwood PM, et al.1997.A family of secreted proteins contains homology to thecysteine-rich ligand-binding domain of frizzled receptors[J]. FEBS.417:385–389
Richard Maganga, Natalie Giles, Katharine Adcroft, et al.2008.Secreted Frizzled related protein-4(sFRP4) promotes epidermal differentiation and apoptosis [J]. Biochemical and Biophysical ResearchCommunications.377:606–611
Rika Nakanishi, Motoyuki Shimizu, Masayuki Mori, et al.2006.Secreted Frizzled-Related Protein4Is aNegative Regulator of Peak BMD in SAMP6Mice[J]. of Bone and Mineral Research.21:1713–1721
Risinger JI, Maxwell GL, Chandramouli GV, et al.2005. Gene expression profiling of microsatelliteunstable and microsatellite stable endometrial cancers indicates distinct pathways of aberrant signaling.Cancer Res.65:5031-5037.
Rodriguez AM, Pisani D, Dechesne CA et al.2005.Transplantation of a multipotent cell population fromhuman adipose tissue induces dystrophin expression in the immunocompetent mdx mouse. J Exp Med.201:1397–1405.
Romaker D, Puetz M, Teschner S, et al.2009. Increased Expression of Secreted Frizzled-Related Protein4in Polycystic Kidneys [J] J Am Soc Nephrol.20:48–56
Rosen ED, Sarraf P, Troy AE, et al.1999.PPAR gamma is required for the differentiation of adipose tissuein viro andin vitro.Mol cell.4:611-617
Roth W, et al.2000.Secreted Frizzled-related proteins inhibit motility and promote growth of humanmalignant glioma cells. Oncogene.19:4210-4220.
Ryden M, Jocken J, van Harmelen V, et al.2007.Comparative studies of the role of hormones ensitivelipase and adipose trigl yceride l i pase in human fat cell lipol ysi s [J]. Am J Physi ol EndocrinolMetab,292: E1847-1855
S Tominaga, T Yamaguchi, S Takahashi, et al.2005. Negative regulation of adipogenesis from humanmesenchymal stem cells by Jun N-terminal kinase, Biochem. Biophys. Res. Commun.326:499–504.
Schumann H, Holtz J, Zerkowski HR et al.2000. Expression of secreted frizzled related proteins3and4inhuman ventricular myocardium correlates with apoptosis related gene expression [J]. Cardiovasc Res.45:720-728
Seema Kumar, Alexey Leontovich, Michael J Coenen, et al.2005.Gene Expression Profiling of OrbitalAdipose Tissue from Patients with Graves’ Ophthalmopathy: A Potential Role for SecretedFrizzled-Related Protein-1in Orbital Adipogenesis [J]. The Journal of Clinical Endocrinology&Metabolism.90:4730–4735
Suzuki H, Watkins DN, Jair KW, et al.2004. Epigenetic inactivation of SFRP genes allows constitutiveWNT signaling in colorectal cancer [J].Nat Genet.36:417-422
Suzuki S, Sembon S, Iwamoto M, et al.2008.Identification of genes downregulated during differentiation ofporcine mesenteric [J]. ANIM SCI.86:3367-3376.
Thecla Constantinou, Fabrizio Baumann, Markus D Lacher,et al.2004.SFRP-4abrogates Wnt-3a-inducedβ-catenin and Akt/PKB; obesity. Cell. Mol. Life Sci.67:1277-1292.
Ting AH, Suzuki H, Cope L, et al.2008.A Requirement for DICER to Maintain Full Promoter CpG IslandHypermethylation in Human Cancer Cells [J]. Cancer Res.68:2570–2575
Tominaga S, Yamaguchi T, Takahashi S, et al.2005.Negative regulation of adipogenesis from humanmesenchymal stem cells by Jun N-terminal kinase [J], Biochem Biophys Res Commun.326:499-504
Tontonoz P, Hu E, Spiegelman BM.1994.Stimulation of adiopgenesis in fibroblasts by PPARgamma2,alipid-activated transcription factor.Cell.79:1147-1156
Toshio M, Tanaka, Hironobu S, et al.2005. Myeloma cells suppress bone formation by secreting a solubleWnt inhibitor, sFRP-2[J].Blood.106:3160-3165
Tuncman G, Hir osumi J, Solinas G, et al.2003.Functi onal in vivo in2teractions bet ween JNK1and JNK2is oforms in obesity and insulin resistance[J]. Proc NatlAcad Sci USA.103:107412-10746.
Turashvili G, Bouchal J, Burkadze G, et al.2003. Wnt signaling pathway in mammary gland developmentand carcinogenesis. Pathobiology.73:213-23.
V Mohsen-Kanson, T Ladoux, A Elabd C. et al.2010. Activin A plays a critical role in proliferation anddifferentiation of human adipose progenitors. Diabetes.59:2513-2521.
Valet P, Tavernier G, Castan-Laurell I et al.2002.Understanding adipose tissue development from transgenicanimal models. J Lipid Res.43:835–860.
Wabitsch M, Brenner RE, Melzner I, et al.2001.Characterization of a human preadipocyte cell strain withhigh capacity for adipose differentiation. Int J Obes Relat Metab Disord.25:8–15.
Wabitsch M, Bruderlein S, Melzner I, et al.2000. Lisa-2, a novel human liposarcoma cell line with a highcapacity for terminal adipose differentiation. Int J Cancer.88:889–894.
Wang S P, Laurin N, Himms Hagen J, e t al.2001.The adipose t is sue phenotype of hormone sensitivelipase deficiency in mice [J]. Obes Res.9:119-128
Wang S, Krinks M, Lin K, et al.1997. Frzb, a Secreted Protein Expressed in the Spemann Organizer, Bindsand Inhibits Wnt-8[J].Cell.88:757-766
Wang YX, Lee CH, Tiep S, et al.2003. Peroxisome-proliferator-activated receptor delta activates fatmetabolism to prevent obesity.cell.113:159-170
White L, Suganthini G, Friis R, et al.2009. Expression of secreted frizzled-related protein4in the primateplacenta[J]. Reprod Biomed Online.18:104–111
Widberg CH, Newell FS, Bachmann A. et al.2009. Fibroblast growth factor receptor1is a key regulator ofearly adipogenic events in human preadipocytes. Am. J. Physiol. Endocrinol.Metab.296:E121-E131.
Yam JWP, Chan KW, Ngan ESW, et al.2005. Genomic structure, alternative splicing and tissue expressionof rFrp/sFRP-4, the rat frizzled related protein gene [J]. Gene.357:55–62
Yeaman,SJ.1990.Hormone-sensitive lipase-a multipurpose enzyme in lipid metabolism[J].BiochimBiophys Acta.1052:128-132
Zamani N. and Brown CW.2010. Emerging roles for the transforming growth factor-beta superfamily inregulating adiposity and energy expenditure. Endocr. Rev.32:387-403.
Zhang Y, Chen FQ, Sun YH et al.2011.Effects of DNMT1silencing on malignant phenotype andmethylated gene expression in cervical cancer cells [J]. J Exp Clin Cancer Res.30:98
Zilberfarb V, Pietri-Rouxel F, Jockers R, et al.1997. Human immortalized brown adipocytes expressfunctional beta3-adrenoceptor coupled to lipolysis. J Cell Sci.110:801–807.
Zizola CF, Frey SK, Jitngarmkusol, S, et al.2010. Cellular retinol-binding protein type I (CRBP-I)regulates adipogenesis. Mol. Cell.Biol.30:3412-3420.
Zou H, Molina JR, Harrington JJ, et al.2010.Aberrant methylation of secreted frizzled-related proteingenes in esophageal adenocarcinoma and Barrett's esophagus. Int J Cancer.116(4):584-91.
Zú iga LA, Shen WJ, Joyce-Shaikh B, et al.2010. IL-17regulates adipogenesis, glucose homeostasis, andobesity. J.Immunol.185:6947-6959.