激活素A促炎作用研究
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摘要
激活素A(Activin A)又称免疫抑制素P,属于转化生长因子-β(TGF-β)超家族成员,具有多种生物学作用,但有关激活素A对参与炎症应答的细胞直接作用,仍缺乏明确报道。本研究通过激活素A体内外刺激小鼠腹腔巨噬细胞及纤维母细胞系L929细胞,探讨激活素A对炎性细胞的直接作用。
研究结果显示,激活素A在体内外均能刺激小鼠腹腔巨噬细胞IL-1β及IL-6分泌,还能增强小鼠腹腔巨噬细胞吞噬和吞饮功能。流式细胞术分析表明,激活素A在体内外对小鼠腹腔巨噬细胞MHCⅠ、MHCⅡ类分子表达均无明显影响,但明显上调巨噬细胞活化标志之一的CD86表达。进一步研究显示,与Ⅰ型巨噬细胞(M1)激动剂细菌内毒素脂多糖(LPS)相比,激活素A明显上调Ⅱ型巨噬细胞(M2)标志精氨酸酶1(Arginase 1)的表达。研究还发现激活素A能够显著提高L929细胞NO、TNFα分泌水平,促进L929细胞吞饮活性以及纤维连结蛋白FN表达,但对L929细胞增殖活性没有影响。上述资料表明,激活素A作为一种促炎症因子,对巨噬细胞以及纤维母细胞系L929细胞活化均有诱导作用;激活素A可能通过增强具有调节作用的Ⅱ型巨噬细胞分泌细胞因子、吞噬活性,提高巨噬细胞参与机体天然免疫应答的能力,但对巨噬细胞抗原提呈作用无影响,可能在机体早期防御中发挥重要作用。
Inflammation is a common disease, and a normal pathological phenomena. When various kinds of pathogenic factors stimulated, the cells, cytokines, extracellular matrix interacted with each other. They could induce the tissues injury or fibroblast cells hyperplasy, then induced tissues and organs fibrosis. The continued development of inflammation can induce organs disorganization and dysfunction, and even failure. It is a serious threaten to humans life and health. Therefore it will be great significance to actively researched for the development of inflammatory mechanisms, and effective treatment to reduce organs disorganization, dysfunction or failure.
Activin A, also known as immunosuppressive P, belongs to transforming growth factor-β(TGF-β) superfamily members, and has many biological effects, but the direct role of activin A on inflammatory response cells still has no clear report. In this study, we used activin A to stimulate L929 fibroblast cell line and mouse peritoneal macrophages in vitro and vivo, and to investigate on the direct role of activin A on inflammatory cells.
Ⅰ. Materials and Methods
1. Animals: 18-22g male C57BL/6 mice.
2. Cell: L929 cells from mouse lung fibroblast cell line.
3. Detected the secretion of activin A in mouse peritoneal macrophages
Primary cultured mouse peritoneal macrophages, LPS(1μg/ml) was used to stimulate the cell. The cells cultured medium alone as control. The supernatants of 1,2,4,8-hour cell cultured was collected, then ELISA method was used to test levels of Activin A in supernatants.
4. Quantitative Analysis of IL-1β, IL-6
Mouse peritoneal macrophages were cultured in medium include Activin A (2～10 ng/ml) 24 h, ELISA detected the IL-1βand IL-6.
5. Analysis the pinocytotic activity of macrophage in vitro.
Mouse peritoneal macrophages cultured in the 96wells plate.Activin A (2～10 ng/ml) stimulated the cells overnight, then added 0.7% neutral red to culture 1 h, PBS wash cells three times, and measured the luminous absorption value (A490nm).
6. Analysis the phagocytic activity of macrophage in vitro.
Mouse peritoneal macrophages cultured in the 96wells plate.Activin A (2～10 ng/ml) stimulated the cells overnight, then added 50μl 2% chicken red blood cell to culture 2 h, PBS rinse, Wright - Giemsa staining, observed by optical microscope.
7. Detection the expression of arginase 1 (Arginase 1), MHCⅠ, MHCⅡand CD86 by flow cytometry.
Mouse peritoneal macrophages cultured in the 12-wells plate. Activin A (10 ng/ml) stimulated the cells overnight , expression of. cell surface molecules of the macrophages were detected by flow cytometry.
8. RT-PCR detection of iNOS mRNA expression
Mouse peritoneal macrophages cultured in the 12-wells plate. Activin A (10 ng/ml) stimulated the cells overnight , RT-PCR was used to detect the expression of iNOS mRNA.
9. Proliferation of mouse peritoneal macrophages
Mouse peritoneal macrophages cultured in the 12-wells plate. Activin A (10 ng/ml) stimulated the cells 24h, MTT method was used to analysis the proliferative ability of primary cultured macrophages, 570 nm absorption was test.
10. Analysis the secretion of cytokines in vivo
Activin A (10 ng and 20 ng) was injected in abdominal cavity, the peritoneal fluid recovered after 24h, then determined the IL-1βand IL-6.
11. Analysis the phagocytic activity of mouse peritoneal macrophage in vivo
The chicken red blood cells was injected in abdominal cavity, then tested the ability of macrophages phagocytose particulate antigen influenced by activin A (10 ng and 20 ng) in vivo.
12. Analysis the expression of CD86 in mouse peritoneal macrophages
Activin A (10 ng and 20 ng) was injected in abdominal cavity, the peritoneal macrophages recovered after 24h, flow cytometry was used to test the expression of CD86 in mouse peritoneal macrophages.
13. Detection the release of NO and TNFa in L929 cells
The different doses of activin A were used to stimulate L929 cells, then tested the level of NO and TNFa.
14. The expression of FN and TIMP mRNA in L929 cells
Activin A stimulated L929 cells, two-step RT-PCR was used to detect the expression of FN and TIMP mRNA.GAPDH as internal reference.
15. Determination of pinocytotic activity of L929 cell stimulated by Activin A
Soluble neutral red dye was used to detect the pinocytotic activity of L929 cells stimulated by activin A.
16. Determination the proliferation of L929 cell
L929 cells cultured in the 96-wells plate, then added activin A (0.8～10 ng/ml) to culture 24h, MTT method was used to analysis the proliferative ability of primary cultured macrophages, 570 nm absorption was test.
Ⅱ. Results
1. LPS induced the secretion of activin A in the primary cultured mouse peritoneal macrophage
LPS stimulated mouse peritoneal macrophages after 4h, the secretion of Activin A rapidly increased, it suggested that activin A may be participate the regulation of macrophage activity in autocrine/paracrine forms.
2. Activin A facilitated the secretion of IL-1βand IL-6 in primary cultured mouse peritoneal macrophage
The direction effect of Activin A can induce IL-1βand IL-6 secretion, and had a dose-dependent manner in mouse peritoneal macrophages.
3. Activin A induced pinocytotic and phagocytic activity of primary cultured mouse peritoneal macrophages
In mouse peritoneal macrophages, Activin A could not only promote pinocytotic activity of macrophage, but also phagocytose the chicken red blood cells.
4. The expression of MHCⅠ, MHCⅡand CD86 influenced by Activin
A in primary cultured mouse peritoneal macrophages The macrophages that Activin A treated, the expression of MHCⅠand MHCⅡdid not change. However, the expression of CD86 was significantly increased.
5. Activin A influenced the proliferation of primary cultured mouse peritoneal macrophages in vitro
Activin A did not significantly affect the proliferation of mouse macrophages.
6. Activin A promoted the activity of peritoneal macrophages in mice in vivo
Activin A can induce the secretion of IL-1βand IL-6 in mouse peritoneal macrophages, and facilitate the phagocytic capacity of mouse peritoneal macrophages.
7. Activin A promoted the expression of CD86 in mouse peritoneal macrophages in vivo
Activin A can increase the expression of CD86 one of the activated hallmarks of mouse peritoneal macrophages.
8. Activin A induced activation of typeⅡmacrophages
The results showed that, LPS can significantly increase the expression of iNOS mRNA, and activin A significantly increase the expression of Arginase 1. The data suggested that activin A may have a selective-induced the activation of M2, through promoting the phagocytic activity of M2 to attend the early response of natural immune response. but did not affect the expression of MHCⅠandⅡ. The results suggest that activin A may not attend the antigen-presenting process of specific immune response.
9. Activin A promote the release of NO and TNFa in L929 cells Activin A has a significant promoted role for secretion of NO and
TNFαin L929 cells.
10. The regulation of activin A about the expression of FN and TIMP mRNA in L929 cells
Activin A significantly increased the expression of FN mRNA, but did not affect the expression of TIMP mRNA. Activin A may be prompted the generation of extracellular matrix, and participate in tissue fibrosis, but may not affect the degradation of extracellular matrix.
11 Activin A influenced the pinocytotic activity of L929 cell
The experimental results show that L929 cells may intake the soluble substances through pinocytotic way, and activin A can promote the L929 cells pinocytotic capacity.
12 Activin A influenced the proliferation of L929 cells Activin A did not affect the proliferation of L929 cells. The results suggested that activin A promote the secretion of inflammatory mediators in L929 cells and the expression of FN mRNA, but didinot influenced the proliferation of L929 cell.
Ⅲ. The conclusions
In conclusion, as a kind of inflammation factor, Activin A could induce the macrophage activation which participated inflammatory response. By means of enhancing the macrophage phagosytosis, promoting the macrophage to take part in the organ innade immune response, Activin A could also play a key role in the early phase of organ defense. As
a multifunction factor, Activin A could promote the L929 to secret the inflammation factors and Cell Extra Medium, which further confirmed as a kind of inflammation factors, Activin A may also play an important part in the development of inflammation and tissue fibration.
研究结果显示,激活素A在体内外均能刺激小鼠腹腔巨噬细胞IL-1β及IL-6分泌,还能增强小鼠腹腔巨噬细胞吞噬和吞饮功能。流式细胞术分析表明,激活素A在体内外对小鼠腹腔巨噬细胞MHCⅠ、MHCⅡ类分子表达均无明显影响,但明显上调巨噬细胞活化标志之一的CD86表达。进一步研究显示,与Ⅰ型巨噬细胞(M1)激动剂细菌内毒素脂多糖(LPS)相比,激活素A明显上调Ⅱ型巨噬细胞(M2)标志精氨酸酶1(Arginase 1)的表达。研究还发现激活素A能够显著提高L929细胞NO、TNFα分泌水平,促进L929细胞吞饮活性以及纤维连结蛋白FN表达,但对L929细胞增殖活性没有影响。上述资料表明,激活素A作为一种促炎症因子,对巨噬细胞以及纤维母细胞系L929细胞活化均有诱导作用;激活素A可能通过增强具有调节作用的Ⅱ型巨噬细胞分泌细胞因子、吞噬活性,提高巨噬细胞参与机体天然免疫应答的能力,但对巨噬细胞抗原提呈作用无影响,可能在机体早期防御中发挥重要作用。
Inflammation is a common disease, and a normal pathological phenomena. When various kinds of pathogenic factors stimulated, the cells, cytokines, extracellular matrix interacted with each other. They could induce the tissues injury or fibroblast cells hyperplasy, then induced tissues and organs fibrosis. The continued development of inflammation can induce organs disorganization and dysfunction, and even failure. It is a serious threaten to humans life and health. Therefore it will be great significance to actively researched for the development of inflammatory mechanisms, and effective treatment to reduce organs disorganization, dysfunction or failure.
Activin A, also known as immunosuppressive P, belongs to transforming growth factor-β(TGF-β) superfamily members, and has many biological effects, but the direct role of activin A on inflammatory response cells still has no clear report. In this study, we used activin A to stimulate L929 fibroblast cell line and mouse peritoneal macrophages in vitro and vivo, and to investigate on the direct role of activin A on inflammatory cells.
Ⅰ. Materials and Methods
1. Animals: 18-22g male C57BL/6 mice.
2. Cell: L929 cells from mouse lung fibroblast cell line.
3. Detected the secretion of activin A in mouse peritoneal macrophages
Primary cultured mouse peritoneal macrophages, LPS(1μg/ml) was used to stimulate the cell. The cells cultured medium alone as control. The supernatants of 1,2,4,8-hour cell cultured was collected, then ELISA method was used to test levels of Activin A in supernatants.
4. Quantitative Analysis of IL-1β, IL-6
Mouse peritoneal macrophages were cultured in medium include Activin A (2～10 ng/ml) 24 h, ELISA detected the IL-1βand IL-6.
5. Analysis the pinocytotic activity of macrophage in vitro.
Mouse peritoneal macrophages cultured in the 96wells plate.Activin A (2～10 ng/ml) stimulated the cells overnight, then added 0.7% neutral red to culture 1 h, PBS wash cells three times, and measured the luminous absorption value (A490nm).
6. Analysis the phagocytic activity of macrophage in vitro.
Mouse peritoneal macrophages cultured in the 96wells plate.Activin A (2～10 ng/ml) stimulated the cells overnight, then added 50μl 2% chicken red blood cell to culture 2 h, PBS rinse, Wright - Giemsa staining, observed by optical microscope.
7. Detection the expression of arginase 1 (Arginase 1), MHCⅠ, MHCⅡand CD86 by flow cytometry.
Mouse peritoneal macrophages cultured in the 12-wells plate. Activin A (10 ng/ml) stimulated the cells overnight , expression of. cell surface molecules of the macrophages were detected by flow cytometry.
8. RT-PCR detection of iNOS mRNA expression
Mouse peritoneal macrophages cultured in the 12-wells plate. Activin A (10 ng/ml) stimulated the cells overnight , RT-PCR was used to detect the expression of iNOS mRNA.
9. Proliferation of mouse peritoneal macrophages
Mouse peritoneal macrophages cultured in the 12-wells plate. Activin A (10 ng/ml) stimulated the cells 24h, MTT method was used to analysis the proliferative ability of primary cultured macrophages, 570 nm absorption was test.
10. Analysis the secretion of cytokines in vivo
Activin A (10 ng and 20 ng) was injected in abdominal cavity, the peritoneal fluid recovered after 24h, then determined the IL-1βand IL-6.
11. Analysis the phagocytic activity of mouse peritoneal macrophage in vivo
The chicken red blood cells was injected in abdominal cavity, then tested the ability of macrophages phagocytose particulate antigen influenced by activin A (10 ng and 20 ng) in vivo.
12. Analysis the expression of CD86 in mouse peritoneal macrophages
Activin A (10 ng and 20 ng) was injected in abdominal cavity, the peritoneal macrophages recovered after 24h, flow cytometry was used to test the expression of CD86 in mouse peritoneal macrophages.
13. Detection the release of NO and TNFa in L929 cells
The different doses of activin A were used to stimulate L929 cells, then tested the level of NO and TNFa.
14. The expression of FN and TIMP mRNA in L929 cells
Activin A stimulated L929 cells, two-step RT-PCR was used to detect the expression of FN and TIMP mRNA.GAPDH as internal reference.
15. Determination of pinocytotic activity of L929 cell stimulated by Activin A
Soluble neutral red dye was used to detect the pinocytotic activity of L929 cells stimulated by activin A.
16. Determination the proliferation of L929 cell
L929 cells cultured in the 96-wells plate, then added activin A (0.8～10 ng/ml) to culture 24h, MTT method was used to analysis the proliferative ability of primary cultured macrophages, 570 nm absorption was test.
Ⅱ. Results
1. LPS induced the secretion of activin A in the primary cultured mouse peritoneal macrophage
LPS stimulated mouse peritoneal macrophages after 4h, the secretion of Activin A rapidly increased, it suggested that activin A may be participate the regulation of macrophage activity in autocrine/paracrine forms.
2. Activin A facilitated the secretion of IL-1βand IL-6 in primary cultured mouse peritoneal macrophage
The direction effect of Activin A can induce IL-1βand IL-6 secretion, and had a dose-dependent manner in mouse peritoneal macrophages.
3. Activin A induced pinocytotic and phagocytic activity of primary cultured mouse peritoneal macrophages
In mouse peritoneal macrophages, Activin A could not only promote pinocytotic activity of macrophage, but also phagocytose the chicken red blood cells.
4. The expression of MHCⅠ, MHCⅡand CD86 influenced by Activin
A in primary cultured mouse peritoneal macrophages The macrophages that Activin A treated, the expression of MHCⅠand MHCⅡdid not change. However, the expression of CD86 was significantly increased.
5. Activin A influenced the proliferation of primary cultured mouse peritoneal macrophages in vitro
Activin A did not significantly affect the proliferation of mouse macrophages.
6. Activin A promoted the activity of peritoneal macrophages in mice in vivo
Activin A can induce the secretion of IL-1βand IL-6 in mouse peritoneal macrophages, and facilitate the phagocytic capacity of mouse peritoneal macrophages.
7. Activin A promoted the expression of CD86 in mouse peritoneal macrophages in vivo
Activin A can increase the expression of CD86 one of the activated hallmarks of mouse peritoneal macrophages.
8. Activin A induced activation of typeⅡmacrophages
The results showed that, LPS can significantly increase the expression of iNOS mRNA, and activin A significantly increase the expression of Arginase 1. The data suggested that activin A may have a selective-induced the activation of M2, through promoting the phagocytic activity of M2 to attend the early response of natural immune response. but did not affect the expression of MHCⅠandⅡ. The results suggest that activin A may not attend the antigen-presenting process of specific immune response.
9. Activin A promote the release of NO and TNFa in L929 cells Activin A has a significant promoted role for secretion of NO and
TNFαin L929 cells.
10. The regulation of activin A about the expression of FN and TIMP mRNA in L929 cells
Activin A significantly increased the expression of FN mRNA, but did not affect the expression of TIMP mRNA. Activin A may be prompted the generation of extracellular matrix, and participate in tissue fibrosis, but may not affect the degradation of extracellular matrix.
11 Activin A influenced the pinocytotic activity of L929 cell
The experimental results show that L929 cells may intake the soluble substances through pinocytotic way, and activin A can promote the L929 cells pinocytotic capacity.
12 Activin A influenced the proliferation of L929 cells Activin A did not affect the proliferation of L929 cells. The results suggested that activin A promote the secretion of inflammatory mediators in L929 cells and the expression of FN mRNA, but didinot influenced the proliferation of L929 cell.
Ⅲ. The conclusions
In conclusion, as a kind of inflammation factor, Activin A could induce the macrophage activation which participated inflammatory response. By means of enhancing the macrophage phagosytosis, promoting the macrophage to take part in the organ innade immune response, Activin A could also play a key role in the early phase of organ defense. As
a multifunction factor, Activin A could promote the L929 to secret the inflammation factors and Cell Extra Medium, which further confirmed as a kind of inflammation factors, Activin A may also play an important part in the development of inflammation and tissue fibration.
引文
[1] Brosh N, Sternberg D, Honigwachs-Sha'anani J, et al. The plasmacytoma growth inhibitor restrictin-P is an antagonist of interleukin 6 and interleukin 11. Identification as a stroma-derived activin A. J Biol Chem, 1995, 270(49): 29594-29600.
[2] Sugiyama M, Ichida T, Sato T, et al. Expression of activin A is increased in cirrhotic and fibrotic rat livers. Gastroenterology, 1998, 114(3): 550-558.
[3]Keelan JA, Zhou Rou, Evans LW, et al. Regulation of activin A, inhibin A, and follistatin production in human amnion and choriodecidual explants by inflammatory mediators. J Soc Gynecol Ivesting, 2000, 7(5): 291-296.
[4]Jones KL, de Kretser DM, Patella S, et al. Activin A and follistatin in systemic inflammation. Mol Cell Endocrinol, 2004, 225(2): 119–125.
[5]Werner S, Alzheimer C. Roles of activin in tissue repair, fibrosis, and inflammatory disease. Cytokine Growth Factor Rev, 2006;17(3):157-71.
[6]Patella S, Phillips DJ, Tchongue J, et al. Follistatin attenuates early liver fibrosis: effects on hepatic stellate cellactivation and hepatocyte apoptosis. Am J Physical Gastrointest Liver Physiol 2006; 290(1): G137–44.
[7]Heldin C H, Miyazono K, ten Dijke P. TGF-βsignaling from cell membrane to nucleus through SMAD proteins,Nature, 1997,390:465-471.
[8]Vale W, Rivier J, Vaughan J , et al. Purification and characterization of an from porcine follicular fluid [J]. Nature,1986;321(6072):776-779.
[9]Ling N, Ying SY, Vaughan J, et al. Pituitary FSH is re-leased by a heterodimer of the beta-subunits from the two forms of inhibin [J]. Nature, 1986,321(6072):779-782.
[10]Dyson S, Gurdon JB. The interpretation of position in a morphogen gradient as revealed by occupancy of activin receptors. Cell 1998; 93: 557-568.
[11]Attisano L, Wrana JL, Cheifetz S, et al. Novel activin receptors: distinct genes and alternative mRNA splicing generate a repertoire of serine/threonine kinase receptors. Cell 1992; 68: 97-108.
[12]Atttisno L, Carcamo J, Ventura F, et al. Identification of human activin and TGF-βtypeⅠreceptors that from heteromeric kinase complexes with typeⅡreceptors . Cell 1993; 75: 671-680.
[13]Carcamo J, Weis FM, Ventura F, et al. TypeⅠreceptors specifygrowth-inhibitory and transcriptional responses to transforming growth factorβand activin. Mol Cell Biol 1994; 14: 3810-3821.
[14]Xu J, Mckeehan K, Matsuzaki K, et al. Inhibin antagonizes inhibition of liver cell growth by activin by a dominant-negative mechanism. J Biol Chem 1995; 270: 6308-6313.
[15]Hashimoto O, Yamoto K, Koseki T, et al. The role of activin typeⅠreceptors in activin A-induced growth arrest and apoptosis in mouse B-cell hybridoma cells. Cell Signal 1998; 10: 743-749.
[16]Massague J. and Chen YG. Controlling TGF-beta signaling. Genes Dev 2000; 14: 627-644.
[17]Ishisaki A, Yamato K, Nakao A, et al. Smad7 is an activin-indu-cible inhibitor of activin-induced growth arrest and apoptosis in mouse B cells[J]. J Biol Chem, 1998,273(38): 24293-24296.
[18]Nagarajan RP, Zhang J, Li W, et al. Regulation of Smad7 promoter by direct association with Smad3 and Smad4. J Biol Chem, 1999, 274(47) : 33412-33418.
[19]liu ZH, Shintani Y, Wakatsuki M, et al. Regulation of immunoreactive activin A secretion from cultured rat anterior pituitary cells. Endocrine J 1996,43(1):39-44.
[20]Liu ZH, Shintani Y, Wakatsuki M, et al.Regulation of immunoreactive activin A secretion from cultured rat anteriorpituitary cells. J Endocrine. 1996;43(1):39–44.
[21]Zhang XJ, Li Y, Tai GX, et al. Effects of activin A on the activities of mouse peritoneal macrophages. Cell. Mol. Immunology 2005;2(1):63-67.
[22]Zhang HJ, Tai GX, Zhou J, et al. Regulation of activin receptor-interacting protein 2 expression in mouse hepatoma Hepa1-6 cells and its relationship with collagentype IV. World J Gastroenterol 2007;13(41):5501-5505.
[23]Shoji H, Tsuchida K, Kishi H, et al.Identification and characterization of a PDZ protein that interacts with activin typesⅡreceptors. J Bol Chem 2000;275(8):5485-5492.
[24]Matsuzaki T, Hanai S, Kishi H, et al. Regulation of endocytosis of activin typeⅡreceptors by a novel PDZ protein through Ral/Ral-binding protein 1-dependent pathway. J Biol Chem 2002;277(21):19008-19018.
[25]Liu ZH, Tsuchida K, Matsuzaki T, et al.Characterization of isoforms of activin receptor–interacting protein 2 that augment activin signaling. J Endocrinol 2006; 189(2):409–421.
[26]Cui X, Tai G, Zhang H, et al. Cloning of the full-length gene of activin receptor-interacting protein2a and characterization of its interaction with ActRⅡA. Prog in Natural Science 2007;17(2):172-176.
[27]Liu HY, Chen FF, Ge JY, et al.Expression and localization of activin receptor- interacting protein 2 in mouse tissues. Gen Comp Endocrinol 2009; 161(2):276-282.
[28]台桂香,徐桂月,劳凤学,等.激活素受体相互作用蛋白在海马神经细胞中的表达及其作用.中国生物制品学杂志2005;18(2):97-100.
[29]刘海岩,葛敬岩,台桂香,等.激活素受体相互作用蛋白1在小鼠组织的表达与分布研究.动物学杂志2008;43(1):26-30.
[30]刘海岩,陈芳芳,高振平,等.ARIP1,2 mRNA及其蛋白在小鼠脑组织表达和分布的比较研究.中风与神经疾病杂志2008;25(6):663-665.
[31]方琳,刘海岩,崔雪玲,等.抗激活素受体相互作用蛋白1抗体的制备及应用.吉林大学学报(医学版)2008;34(1):11-13.
[32]Mather JP, Moore A, Li RH. Activins, inhibins, and follista- tins: further thoughts on a growing family of regulators.Proc Soc Exp Biol Med. 1997 Jul;215(3):209-22.
[33]Ying SY.Inhibins, activins, and follistatins: gonadal proteins modulating the secretion of follicle-stimulating hormone. Endocr Rev. 1988 May;9(2):267-93.
[34]Yoshikawa SI, Aota S, Shirayoshi Y, et al.The ActR-I activin receptor protein is expressed in notochord, lens placode and pituitary primordium cells in the mouse embryo.Mech Dev. 2000 Mar 1;91(1-2):439-44.
[35]Lee S, Rivier C. Effect of repeated activin-A treatment on the activity of the hypothalamic-pituitary-gonadal axis of the adult male rat. Biol Reprod. 1997 Apr;56(4):969-75.
[36]Munro LM, Kennedy A, McNicol AM. The expression of inhibin/ activin subunits in the human adrenal cortex and its tumours. J Endocrinol. 1999 May;161(2):341-7.
[37]Keating DJ, Chen C. Activin A stimulates catecholamine secretion from rat adrenal chromaffin cells: a new physiological mechanism. J Endocrinol. 2005 Aug;186(2):R1-5. Links.
[38]Beuschlein F, Looyenga BD, Reincke M, et al. Role of the inhibin/activin system and luteinizing hormone in adrenocortical tumorigenesis.Horm Metab Res. 2004 Jun;36(6):392-6.
[39]Wang EY, Ma EY, Woodruff TK. Activin signal transduction in the fetal rat adrenal gland and in human H295R cells.J Endocrinol. 2003 Jul;178(1):137-48.
[40]V?nttinen T, Liu J, Kuulasmaa T, et al.Expression of activin/inhibin signaling components in the human adrenal gland and the effects of activins and inhibins on adrenocortical steroidogenesis and apoptosis.J Endocrinol. 2003 Sep; 178(3):479-89.
[41]Anderson RA, Evans LW, Irvine DS, et al. Follistatin and activin A production by the male reproductive tract. Hum Reprod. 1998Dec;13(12):3319-25.
[42]Ying SY, Zhang Z, Huang G. Expression and localization of inhibin/activin subunits and activin receptors in the normal rat prostate. Life Sci. 1997;60(6):397-401.
[43]Zhang Z, Zhao Y, Batres Y, et al.Regulation of growth and prostatic marker expression by activin A in an androgen-sensitive prostate cancer cell line LNCAP. Biochem Biophys Res Commun. 1997 May 19;234(2):362-5.
[44]Tanaka A, Hasegawa Y, Hakamata Y, et al. Purification of activins from androgen-independent Shionogi carcinoma cells demonstrates enhanced expression of activin betaB-subunit under androgen-depleted cell conditions in vitro and in vivo. J Cell Physiol. 2001 Aug;188(2):194-200.
[45]Dowling CR, Risbridger GP. The role of inhibins and activins in prostate cancer pathogenesis. Endocr Relat Cancer. 2000 Dec;7(4):243-56.
[46]Boitani C, Stefanini M, Fragale A, et al. Activin stimulates Sertoli cell proliferation in a defined period of rat testis development. Endocrinology. 1995 Dec;136(12):5438-44.
[47]Silva JR, van den Hurk R, van Tol HT, et al. Gene expression and protein localisation for activin-A, follistatin and activinreceptors in goat ovaries. J Endocrinol. 2004 Nov;183(2):405-15.
[48]Muttukrishna S, Tannetta D, Groome N, et al. Activin and follistatin in female reproduction. Mol Cell Endocrinol. 2004 Oct 15;225(1-2):45-56.
[49]Martins da Silva SJ, Bayne RA, Cambray N, et al. Expression of activin subunits and receptors in the developing human ovary: activin A promotes germ cell survival and proliferation before primordial follicle formation. Dev Biol. 2004 Feb 15;266(2):334-45.
[50]Zhao J, Taverne MA, van der Weijden GC, et al. Effect of activin A on in vitro development of rat preantral follicles and localization of activin A and activin receptorⅡ. Biol Reprod. 2001 Sep;65(3):967-77.
[51]Mylonas I, Makovitzky J, Shabani N, et al. Development and characterisation of an antibody for the immunohistochemical detection of inhibin/activin betaE (betaE) in normal human ovarian and placental tissue.Acta Histochem. 2009 Feb 3.
[52]Johnson PA, Woodcock JR, Kent TR. Effect of activin A and inhibin A on expression of the inhibin/activin beta-B-subunit and gonadotropin receptors in granulosa cells of the hen. Gen Comp Endocrinol. 2006 Jun;147(2):102-7.
[53]Mabuchi Y, Yamoto M, Minami S, et al.Immunohistochemicallocalization of inhibin and activin subunits, activin receptors, and Smads in ovarian clear cell adenocarcinoma. Oncol Rep. 2006 Feb;15(2):291-6.
[54]张慧娟,刘伯宁,Sanjiv M,等.Inhibin/Aetivin信号对卵巢癌生长调控的初步研究[J].现代妇产科进展,2003,12(l):12-15.
[55]Tanaka T, Toujima S, Otani T, et al. Expression and function of activin receptors in human endometrial adenocarcinoma cells. Int J Oncol. 2003 Sep;23(3):657-63.
[56]Petraglia F, Florio P, Luisi S, et al. Expression and secretion of inhibin and activin in normal and neoplastic uterine tissues. High levels of serum activin A in women with endometrial and cervical carcinoma. J Clin Endocrinol Metab. 1998 Apr;83(4):1194-200.
[57]Troeger C, Holzgreve W, Ladewig A, et al. Examination of maternal plasma erythropoietin and activin A concentrations with regard to circulatory erythroblast levels in normal and preeclamptic pregnancies. Fetal Diagn Ther. 2006;21(1):156-60.
[58]Bussmann UA, Lanuza GM, Bussmann LE. Activin and follistatin in rat mammary gland. Mol Cell Endocrinol. 2004 Jun 30;221(1-2):9-19.
[59]Burdette JE, Jeruss JS, Kurley SJ, et al. Activin A mediates growth inhibition and cell cycle arrest through Smads in human breast cancer cells. Cancer Res. 2005 Sep 1;65(17):7968-75.
[60]Calonaci G, Florio P, Lombardi I, et al. Identification of activin A and follistatin in human milk.Luisi S, Growth Factors. 2002 Sep;20(3):147-50.
[61]Takamura K, Tsuchida K, Miyake H, et al. Activin and activin receptor expression changes in liver regeneration in rat. J Surg Res. 2005 Jun 1;126(1):3-11.
[62]Clotman F, Lemaigre FP. Control of hepatic differentiation by activin/TGFbeta signaling. Cell Cycle. 2006 Jan;5(2):168-71.
[63]Sugiyama M, Ichida T, Sato T, et al.Expression of activin A is increased in cirrhotic and fibrotic rat livers. Gastroenterology. 1998 Mar;114(3):550-8.
[64]La Rosa S, Uccella S, Marchet S, et al. Localization of inhibins and activins in normal endocrine cells and endocrine tumors of the gut and pancreas: an immunohistochemical and in situ hybridization study. J Histochem Cytochem. 2004 Feb;52(2):217-25.
[65]Luisi S, Florio P, Reis FM, et al. Expression and secretion of activin A: possible physiological and clinical implications. Eur J Endocrinol. 2001 Sep;145(3):225-36.
[66]La Rosa S, Uccella S, Billo P, et al. Immunohistochemical localization of alpha- and betaA-subunits of inhibin/activin in human normal endocrine cells and related tumors of the digestive system.Virchows Arch. 1999 Jan;434(1):29-36.
[67]Ohnishi N, Miyata T, Ohnishi H, et al. Activin A is an autocrine activator of rat pancreatic stellate cells: potential therapeutic role of follistatin for pancreatic fibrosis. Gut. 2003 Oct;52(10):1487-93.
[68]Fuller K, Bayley KE, Chambers TJ. Activin A is an essential cofactor for osteoclast induction. Biochem Biophys Res Commun. 2000 Feb 5;268(1):2-7.
[69]Shiozaki M, Eto Y. Function, molecular structure and gene expression regulation of erythroid differentiation factor (EDF/activin A). Nippon Rinsho. 1992 Aug;50(8):1950-5.
[70]Shav-Tal Y, Zipori D. The role of activin a in regulation of hemopoiesis. Stem Cells. 2002;20(6):493-500.
[71]Shiozaki M, Kosaka M, Eto Y. Activin A: a commitment factor in erythroid differentiation. Biochem Biophys Res Commun. 1998 Jan 26; 242(3): 631-5.
[72]Florio P, Perrone S, Luisi S, et al. Activin a plasma levels at birth: an index of fetal hypoxia in preterm newborn[J]. Pediatr Res, 2003, 54(5):696-700.
[73]Phillips D J, Jones K L, Scheerlinck J Y, et al. Evidence for activin A and follistatin involvement in the systemic inflammatoryresponse[J]. Cell Endocrinol, 2001, 180(12):155-162.
[74]Blumen Z, Ritter M. Inhibin, activin, and follistatin in human fetal pituitary and gonadal physiology[J]. Ann N Y Acad Sci, 2001, 943(9):34-48.
[75]Nawa H, Takahashi M, Patterson P H. Cytokine and growth factor involvement in schizophrenia support for the developmental model[J]. Mole Psychia, 2000, 5(6):594-603.
[76]Hughes PE,Alexi T,Williams CE, et al.Administration of recombinant human Activin-A has powerful neurotrophic effects on select striatal phenotypes in the quinolinic acid lesion model of Huntington's disease Neuroscience. 1999;92(1):197-209 .
[77]Fuller K, Bayley KE, Chambers TJ. Activin A is an essential cofactor for osteoclast induction. Biochem Biophys Res Commun. 2000 Feb 5;268(1):2-7.
[78]Sakai R, Eto Y, Ohtsuka M, et al. Activin enhances osteoclast-like cell formation in vitro. Biochem Biophys Res Commun. 1993 Aug 31;195(1):39-46.
[79]Sakai R, Eto Y. Involvement of activin in the regulation of bone metabolism. Mol Cell Endocrinol. 2001 Jun 30;180(1-2):183-8.
[80]Hirotani H, Ohtsuka-Isoya M, Mori S, et al. Activin A increases the bone mass of grafted bone in C3H/HeJ mice. Calcif TissueInt. 2002 Apr; 70(4): 330-8.
[81]Ogawa Y, Schmidt DK, Nathan RM, et al. Bovine bone activin enhances bone morphogenetic protein-induced ectopic bone formation. J Biol Chem. 1992 Jul 15;267(20):14233-7.
[82]Sakai R, Fujita S, Horie T, et al. Activin increases bone mass and mechanical strength of lumbar vertebrae in aged ovariectomized rats. Bone. 2000 Jul;27(1):91-6.
[83]Okuma Y, Saito K, O'Connor AE, et al. Reciprocal regulation of activin A and inhibin B by interleukin-1 (IL-1) and follicle-stimulating hormone (FSH) in rat Sertoli cells in vitro. J Endocrinol. 2005 Apr;185(1):99-110.
[84] Okuma Y, O'Connor AE, Muir JA, et al. Regulation of activin A and inhibin B secretion by inflammatory mediators in adult rat Sertoli cell cultures.J Endocrinol. 2005 Oct;187(1):125-34.
[85]Mitsuhiro MR, Eguchi S, Yamashita H. Regulation mechanisms of retinal pigment epithelial cell migration by the TGF-beta superfamily. Acta Ophthalmol Scand. 2003 Dec;81(6):630-8. Links.
[86]Funaba M, Ikeda T, Ogawa K, et al. Role of activin A in murine mast cells: modulation of cell growth, differentiation, and migration. J Leukoc Biol. 2003 Jun;73(6):793-801.
[87]Yu EW, Dolter KE, Shao LE, et al. Suppression of IL-6biological activities by activin A and implications for inflammatory arthropathies. Clin Exp Immunol. 1998 Apr;112(1):126-32.
[88]Wu DD, Lai M, Hughes PE, et al. Expression of the activin axis and neuronal rescue effects of recombinant activin A following hypoxic-ischemic brain injury in the infant rat. Brain Res. 1999 Jul 24;835(2):369-78.
[89]Tretter YP, Munz B, Hübner G, et al. Strong induction of activin expression after hippocampal lesion. Neuroreport. 1996 Jul 29;7(11):1819-23.
[90]Patel VB,Robbins M A,Topol E J. C- Reactive Protein :a“golden marker”for inflammation and coronary artery disease.Cleve Clin J Med,2001,68(6):521.
[91]Weiss SJ.Comment in.Tissue destruction by neutrophils.N Engl J Med. 1989 Feb 9;320(6):365-76.
[92]Wmi - dms JK, Sukhova GK, Herrington DM, et a1. Pravastatin has cholesterol lowering independent effects on the artery wall of atherosclerotic monkeys. Am J Coil Cardio1 1998; 31: 684 - 691.
[93]VanDer M IM.DeM aat MP. Hak AE.et a1. C- reactive protein predicts progression of atherosclerosis measuredal. rarious sites in the arterial tree: the Rotterdam study.Stroke 2002; 33: 2750.
[94]Pepys MB, Berger A.The renaissance of C - reactive protein.J. BMJ. 2001; 322: 4-5.
[95]Arturo Garcia-Touchard, Timothy D. Henry, Giuseppe Sangiorgi, et al. Extracellular Proteases in Atherosclerosis and Restenosis. Arteriosclerosis, Thrombosis, and Vascular Biology 2005; 25: 1119.
[96]Jones DA, Newham DJ, Round JM, et al.Experimental human muscle damage: morphological changes in relation to other indices of damage.J Physiol. 1986 Jun;375:435-48.
[97]Eckes B, Zigrino P, Kessler D, et al.Fibroblast-matrix interactions in wound healing and fibrosis.Matrix Biol. 2000 Aug;19(4):325-32.
[98]Gabbiani G. The myofibroblast in wound healing and fibro-contractive diseases.J Pathol.2003,200:500-503.
[99]Date M, Matsuzaki K, Matsushita M, et al.Differential regulation of activin A for hepatocyte growth and fibronectin synthesis in rat liver injury. J Hepatol. 2000 Fb;32(2):251-60.
[100]Ohga E, Matsuse T, Teramoto S, et al. Effects of activin A on proliferation and differentiation of human lung fibroblasts. Biochem Biophys Res Commun. 1996 Nov 12;228(2):391-6.
[101] Yan Y, Wanshun L, Baogin H, et al. The antioxidative and immunostimulating properties of D-glucosamine. Int Immunopharmacol, 2007; 7(1): 29-35.
[102]Zhou J, Tai G, Liu H, et al. Activin A down-regulates the phagocytosis of lipopolysaccharide-activated mouse peritoneal macrophages in vitro and in vivo. Cell Immunol 2009; 255(1-2): 69-75.
[103]Chen YG, Lui HM, Lin SL, et al.Regulation of cell proliferation, apoptosis, and carcinogenesis by activin.Exp Biol Med (Maywood). 2002 Feb;227(2):75-87.
[104]Welt C, Sidis Y, Keutmann H, et al. Activins, inhibins, and follistatins: from endocrinology to signaling. A paradigm for the new millennium.Exp Biol Med (Maywood). 2002 Oct;227(9):724-52.
[105] Wang SY, Tai GX, Zhang PY, Mu DP, Zhang XJ, Liu ZH. Inhibitory effect of activin A on activation of lipopolysaccharide-stimulated mouse macrophage RAW264.7 cells. Cytokine 2008; 42(1): 85-89.
[106] Murakamia Y, Shojia M, Hanazawab S, et al. Preventive effect of bis-eugenol, a eugenol ortho dimer on lipopolysaccharide- stimulated nuclear factor kappa B activation and inflammatory cytokine expression in macrophages. Biochem Pharmacol, 2003, 66(6): 1061–1066.
[107] Garrido G, Delgado R, Lemus Y, et al. Protection against septic shock and suppression of tumor necrosis factor alpha and nitric oxide production on macrophages and microglia by a standard aqueousextract of Mangifera indica L. (VIMANG). Role of mangiferin isolated from the extract. Pharmacological Research, 2004, 50(2): 165–172.
[2] Sugiyama M, Ichida T, Sato T, et al. Expression of activin A is increased in cirrhotic and fibrotic rat livers. Gastroenterology, 1998, 114(3): 550-558.
[3]Keelan JA, Zhou Rou, Evans LW, et al. Regulation of activin A, inhibin A, and follistatin production in human amnion and choriodecidual explants by inflammatory mediators. J Soc Gynecol Ivesting, 2000, 7(5): 291-296.
[4]Jones KL, de Kretser DM, Patella S, et al. Activin A and follistatin in systemic inflammation. Mol Cell Endocrinol, 2004, 225(2): 119–125.
[5]Werner S, Alzheimer C. Roles of activin in tissue repair, fibrosis, and inflammatory disease. Cytokine Growth Factor Rev, 2006;17(3):157-71.
[6]Patella S, Phillips DJ, Tchongue J, et al. Follistatin attenuates early liver fibrosis: effects on hepatic stellate cellactivation and hepatocyte apoptosis. Am J Physical Gastrointest Liver Physiol 2006; 290(1): G137–44.
[7]Heldin C H, Miyazono K, ten Dijke P. TGF-βsignaling from cell membrane to nucleus through SMAD proteins,Nature, 1997,390:465-471.
[8]Vale W, Rivier J, Vaughan J , et al. Purification and characterization of an from porcine follicular fluid [J]. Nature,1986;321(6072):776-779.
[9]Ling N, Ying SY, Vaughan J, et al. Pituitary FSH is re-leased by a heterodimer of the beta-subunits from the two forms of inhibin [J]. Nature, 1986,321(6072):779-782.
[10]Dyson S, Gurdon JB. The interpretation of position in a morphogen gradient as revealed by occupancy of activin receptors. Cell 1998; 93: 557-568.
[11]Attisano L, Wrana JL, Cheifetz S, et al. Novel activin receptors: distinct genes and alternative mRNA splicing generate a repertoire of serine/threonine kinase receptors. Cell 1992; 68: 97-108.
[12]Atttisno L, Carcamo J, Ventura F, et al. Identification of human activin and TGF-βtypeⅠreceptors that from heteromeric kinase complexes with typeⅡreceptors . Cell 1993; 75: 671-680.
[13]Carcamo J, Weis FM, Ventura F, et al. TypeⅠreceptors specifygrowth-inhibitory and transcriptional responses to transforming growth factorβand activin. Mol Cell Biol 1994; 14: 3810-3821.
[14]Xu J, Mckeehan K, Matsuzaki K, et al. Inhibin antagonizes inhibition of liver cell growth by activin by a dominant-negative mechanism. J Biol Chem 1995; 270: 6308-6313.
[15]Hashimoto O, Yamoto K, Koseki T, et al. The role of activin typeⅠreceptors in activin A-induced growth arrest and apoptosis in mouse B-cell hybridoma cells. Cell Signal 1998; 10: 743-749.
[16]Massague J. and Chen YG. Controlling TGF-beta signaling. Genes Dev 2000; 14: 627-644.
[17]Ishisaki A, Yamato K, Nakao A, et al. Smad7 is an activin-indu-cible inhibitor of activin-induced growth arrest and apoptosis in mouse B cells[J]. J Biol Chem, 1998,273(38): 24293-24296.
[18]Nagarajan RP, Zhang J, Li W, et al. Regulation of Smad7 promoter by direct association with Smad3 and Smad4. J Biol Chem, 1999, 274(47) : 33412-33418.
[19]liu ZH, Shintani Y, Wakatsuki M, et al. Regulation of immunoreactive activin A secretion from cultured rat anterior pituitary cells. Endocrine J 1996,43(1):39-44.
[20]Liu ZH, Shintani Y, Wakatsuki M, et al.Regulation of immunoreactive activin A secretion from cultured rat anteriorpituitary cells. J Endocrine. 1996;43(1):39–44.
[21]Zhang XJ, Li Y, Tai GX, et al. Effects of activin A on the activities of mouse peritoneal macrophages. Cell. Mol. Immunology 2005;2(1):63-67.
[22]Zhang HJ, Tai GX, Zhou J, et al. Regulation of activin receptor-interacting protein 2 expression in mouse hepatoma Hepa1-6 cells and its relationship with collagentype IV. World J Gastroenterol 2007;13(41):5501-5505.
[23]Shoji H, Tsuchida K, Kishi H, et al.Identification and characterization of a PDZ protein that interacts with activin typesⅡreceptors. J Bol Chem 2000;275(8):5485-5492.
[24]Matsuzaki T, Hanai S, Kishi H, et al. Regulation of endocytosis of activin typeⅡreceptors by a novel PDZ protein through Ral/Ral-binding protein 1-dependent pathway. J Biol Chem 2002;277(21):19008-19018.
[25]Liu ZH, Tsuchida K, Matsuzaki T, et al.Characterization of isoforms of activin receptor–interacting protein 2 that augment activin signaling. J Endocrinol 2006; 189(2):409–421.
[26]Cui X, Tai G, Zhang H, et al. Cloning of the full-length gene of activin receptor-interacting protein2a and characterization of its interaction with ActRⅡA. Prog in Natural Science 2007;17(2):172-176.
[27]Liu HY, Chen FF, Ge JY, et al.Expression and localization of activin receptor- interacting protein 2 in mouse tissues. Gen Comp Endocrinol 2009; 161(2):276-282.
[28]台桂香,徐桂月,劳凤学,等.激活素受体相互作用蛋白在海马神经细胞中的表达及其作用.中国生物制品学杂志2005;18(2):97-100.
[29]刘海岩,葛敬岩,台桂香,等.激活素受体相互作用蛋白1在小鼠组织的表达与分布研究.动物学杂志2008;43(1):26-30.
[30]刘海岩,陈芳芳,高振平,等.ARIP1,2 mRNA及其蛋白在小鼠脑组织表达和分布的比较研究.中风与神经疾病杂志2008;25(6):663-665.
[31]方琳,刘海岩,崔雪玲,等.抗激活素受体相互作用蛋白1抗体的制备及应用.吉林大学学报(医学版)2008;34(1):11-13.
[32]Mather JP, Moore A, Li RH. Activins, inhibins, and follista- tins: further thoughts on a growing family of regulators.Proc Soc Exp Biol Med. 1997 Jul;215(3):209-22.
[33]Ying SY.Inhibins, activins, and follistatins: gonadal proteins modulating the secretion of follicle-stimulating hormone. Endocr Rev. 1988 May;9(2):267-93.
[34]Yoshikawa SI, Aota S, Shirayoshi Y, et al.The ActR-I activin receptor protein is expressed in notochord, lens placode and pituitary primordium cells in the mouse embryo.Mech Dev. 2000 Mar 1;91(1-2):439-44.
[35]Lee S, Rivier C. Effect of repeated activin-A treatment on the activity of the hypothalamic-pituitary-gonadal axis of the adult male rat. Biol Reprod. 1997 Apr;56(4):969-75.
[36]Munro LM, Kennedy A, McNicol AM. The expression of inhibin/ activin subunits in the human adrenal cortex and its tumours. J Endocrinol. 1999 May;161(2):341-7.
[37]Keating DJ, Chen C. Activin A stimulates catecholamine secretion from rat adrenal chromaffin cells: a new physiological mechanism. J Endocrinol. 2005 Aug;186(2):R1-5. Links.
[38]Beuschlein F, Looyenga BD, Reincke M, et al. Role of the inhibin/activin system and luteinizing hormone in adrenocortical tumorigenesis.Horm Metab Res. 2004 Jun;36(6):392-6.
[39]Wang EY, Ma EY, Woodruff TK. Activin signal transduction in the fetal rat adrenal gland and in human H295R cells.J Endocrinol. 2003 Jul;178(1):137-48.
[40]V?nttinen T, Liu J, Kuulasmaa T, et al.Expression of activin/inhibin signaling components in the human adrenal gland and the effects of activins and inhibins on adrenocortical steroidogenesis and apoptosis.J Endocrinol. 2003 Sep; 178(3):479-89.
[41]Anderson RA, Evans LW, Irvine DS, et al. Follistatin and activin A production by the male reproductive tract. Hum Reprod. 1998Dec;13(12):3319-25.
[42]Ying SY, Zhang Z, Huang G. Expression and localization of inhibin/activin subunits and activin receptors in the normal rat prostate. Life Sci. 1997;60(6):397-401.
[43]Zhang Z, Zhao Y, Batres Y, et al.Regulation of growth and prostatic marker expression by activin A in an androgen-sensitive prostate cancer cell line LNCAP. Biochem Biophys Res Commun. 1997 May 19;234(2):362-5.
[44]Tanaka A, Hasegawa Y, Hakamata Y, et al. Purification of activins from androgen-independent Shionogi carcinoma cells demonstrates enhanced expression of activin betaB-subunit under androgen-depleted cell conditions in vitro and in vivo. J Cell Physiol. 2001 Aug;188(2):194-200.
[45]Dowling CR, Risbridger GP. The role of inhibins and activins in prostate cancer pathogenesis. Endocr Relat Cancer. 2000 Dec;7(4):243-56.
[46]Boitani C, Stefanini M, Fragale A, et al. Activin stimulates Sertoli cell proliferation in a defined period of rat testis development. Endocrinology. 1995 Dec;136(12):5438-44.
[47]Silva JR, van den Hurk R, van Tol HT, et al. Gene expression and protein localisation for activin-A, follistatin and activinreceptors in goat ovaries. J Endocrinol. 2004 Nov;183(2):405-15.
[48]Muttukrishna S, Tannetta D, Groome N, et al. Activin and follistatin in female reproduction. Mol Cell Endocrinol. 2004 Oct 15;225(1-2):45-56.
[49]Martins da Silva SJ, Bayne RA, Cambray N, et al. Expression of activin subunits and receptors in the developing human ovary: activin A promotes germ cell survival and proliferation before primordial follicle formation. Dev Biol. 2004 Feb 15;266(2):334-45.
[50]Zhao J, Taverne MA, van der Weijden GC, et al. Effect of activin A on in vitro development of rat preantral follicles and localization of activin A and activin receptorⅡ. Biol Reprod. 2001 Sep;65(3):967-77.
[51]Mylonas I, Makovitzky J, Shabani N, et al. Development and characterisation of an antibody for the immunohistochemical detection of inhibin/activin betaE (betaE) in normal human ovarian and placental tissue.Acta Histochem. 2009 Feb 3.
[52]Johnson PA, Woodcock JR, Kent TR. Effect of activin A and inhibin A on expression of the inhibin/activin beta-B-subunit and gonadotropin receptors in granulosa cells of the hen. Gen Comp Endocrinol. 2006 Jun;147(2):102-7.
[53]Mabuchi Y, Yamoto M, Minami S, et al.Immunohistochemicallocalization of inhibin and activin subunits, activin receptors, and Smads in ovarian clear cell adenocarcinoma. Oncol Rep. 2006 Feb;15(2):291-6.
[54]张慧娟,刘伯宁,Sanjiv M,等.Inhibin/Aetivin信号对卵巢癌生长调控的初步研究[J].现代妇产科进展,2003,12(l):12-15.
[55]Tanaka T, Toujima S, Otani T, et al. Expression and function of activin receptors in human endometrial adenocarcinoma cells. Int J Oncol. 2003 Sep;23(3):657-63.
[56]Petraglia F, Florio P, Luisi S, et al. Expression and secretion of inhibin and activin in normal and neoplastic uterine tissues. High levels of serum activin A in women with endometrial and cervical carcinoma. J Clin Endocrinol Metab. 1998 Apr;83(4):1194-200.
[57]Troeger C, Holzgreve W, Ladewig A, et al. Examination of maternal plasma erythropoietin and activin A concentrations with regard to circulatory erythroblast levels in normal and preeclamptic pregnancies. Fetal Diagn Ther. 2006;21(1):156-60.
[58]Bussmann UA, Lanuza GM, Bussmann LE. Activin and follistatin in rat mammary gland. Mol Cell Endocrinol. 2004 Jun 30;221(1-2):9-19.
[59]Burdette JE, Jeruss JS, Kurley SJ, et al. Activin A mediates growth inhibition and cell cycle arrest through Smads in human breast cancer cells. Cancer Res. 2005 Sep 1;65(17):7968-75.
[60]Calonaci G, Florio P, Lombardi I, et al. Identification of activin A and follistatin in human milk.Luisi S, Growth Factors. 2002 Sep;20(3):147-50.
[61]Takamura K, Tsuchida K, Miyake H, et al. Activin and activin receptor expression changes in liver regeneration in rat. J Surg Res. 2005 Jun 1;126(1):3-11.
[62]Clotman F, Lemaigre FP. Control of hepatic differentiation by activin/TGFbeta signaling. Cell Cycle. 2006 Jan;5(2):168-71.
[63]Sugiyama M, Ichida T, Sato T, et al.Expression of activin A is increased in cirrhotic and fibrotic rat livers. Gastroenterology. 1998 Mar;114(3):550-8.
[64]La Rosa S, Uccella S, Marchet S, et al. Localization of inhibins and activins in normal endocrine cells and endocrine tumors of the gut and pancreas: an immunohistochemical and in situ hybridization study. J Histochem Cytochem. 2004 Feb;52(2):217-25.
[65]Luisi S, Florio P, Reis FM, et al. Expression and secretion of activin A: possible physiological and clinical implications. Eur J Endocrinol. 2001 Sep;145(3):225-36.
[66]La Rosa S, Uccella S, Billo P, et al. Immunohistochemical localization of alpha- and betaA-subunits of inhibin/activin in human normal endocrine cells and related tumors of the digestive system.Virchows Arch. 1999 Jan;434(1):29-36.
[67]Ohnishi N, Miyata T, Ohnishi H, et al. Activin A is an autocrine activator of rat pancreatic stellate cells: potential therapeutic role of follistatin for pancreatic fibrosis. Gut. 2003 Oct;52(10):1487-93.
[68]Fuller K, Bayley KE, Chambers TJ. Activin A is an essential cofactor for osteoclast induction. Biochem Biophys Res Commun. 2000 Feb 5;268(1):2-7.
[69]Shiozaki M, Eto Y. Function, molecular structure and gene expression regulation of erythroid differentiation factor (EDF/activin A). Nippon Rinsho. 1992 Aug;50(8):1950-5.
[70]Shav-Tal Y, Zipori D. The role of activin a in regulation of hemopoiesis. Stem Cells. 2002;20(6):493-500.
[71]Shiozaki M, Kosaka M, Eto Y. Activin A: a commitment factor in erythroid differentiation. Biochem Biophys Res Commun. 1998 Jan 26; 242(3): 631-5.
[72]Florio P, Perrone S, Luisi S, et al. Activin a plasma levels at birth: an index of fetal hypoxia in preterm newborn[J]. Pediatr Res, 2003, 54(5):696-700.
[73]Phillips D J, Jones K L, Scheerlinck J Y, et al. Evidence for activin A and follistatin involvement in the systemic inflammatoryresponse[J]. Cell Endocrinol, 2001, 180(12):155-162.
[74]Blumen Z, Ritter M. Inhibin, activin, and follistatin in human fetal pituitary and gonadal physiology[J]. Ann N Y Acad Sci, 2001, 943(9):34-48.
[75]Nawa H, Takahashi M, Patterson P H. Cytokine and growth factor involvement in schizophrenia support for the developmental model[J]. Mole Psychia, 2000, 5(6):594-603.
[76]Hughes PE,Alexi T,Williams CE, et al.Administration of recombinant human Activin-A has powerful neurotrophic effects on select striatal phenotypes in the quinolinic acid lesion model of Huntington's disease Neuroscience. 1999;92(1):197-209 .
[77]Fuller K, Bayley KE, Chambers TJ. Activin A is an essential cofactor for osteoclast induction. Biochem Biophys Res Commun. 2000 Feb 5;268(1):2-7.
[78]Sakai R, Eto Y, Ohtsuka M, et al. Activin enhances osteoclast-like cell formation in vitro. Biochem Biophys Res Commun. 1993 Aug 31;195(1):39-46.
[79]Sakai R, Eto Y. Involvement of activin in the regulation of bone metabolism. Mol Cell Endocrinol. 2001 Jun 30;180(1-2):183-8.
[80]Hirotani H, Ohtsuka-Isoya M, Mori S, et al. Activin A increases the bone mass of grafted bone in C3H/HeJ mice. Calcif TissueInt. 2002 Apr; 70(4): 330-8.
[81]Ogawa Y, Schmidt DK, Nathan RM, et al. Bovine bone activin enhances bone morphogenetic protein-induced ectopic bone formation. J Biol Chem. 1992 Jul 15;267(20):14233-7.
[82]Sakai R, Fujita S, Horie T, et al. Activin increases bone mass and mechanical strength of lumbar vertebrae in aged ovariectomized rats. Bone. 2000 Jul;27(1):91-6.
[83]Okuma Y, Saito K, O'Connor AE, et al. Reciprocal regulation of activin A and inhibin B by interleukin-1 (IL-1) and follicle-stimulating hormone (FSH) in rat Sertoli cells in vitro. J Endocrinol. 2005 Apr;185(1):99-110.
[84] Okuma Y, O'Connor AE, Muir JA, et al. Regulation of activin A and inhibin B secretion by inflammatory mediators in adult rat Sertoli cell cultures.J Endocrinol. 2005 Oct;187(1):125-34.
[85]Mitsuhiro MR, Eguchi S, Yamashita H. Regulation mechanisms of retinal pigment epithelial cell migration by the TGF-beta superfamily. Acta Ophthalmol Scand. 2003 Dec;81(6):630-8. Links.
[86]Funaba M, Ikeda T, Ogawa K, et al. Role of activin A in murine mast cells: modulation of cell growth, differentiation, and migration. J Leukoc Biol. 2003 Jun;73(6):793-801.
[87]Yu EW, Dolter KE, Shao LE, et al. Suppression of IL-6biological activities by activin A and implications for inflammatory arthropathies. Clin Exp Immunol. 1998 Apr;112(1):126-32.
[88]Wu DD, Lai M, Hughes PE, et al. Expression of the activin axis and neuronal rescue effects of recombinant activin A following hypoxic-ischemic brain injury in the infant rat. Brain Res. 1999 Jul 24;835(2):369-78.
[89]Tretter YP, Munz B, Hübner G, et al. Strong induction of activin expression after hippocampal lesion. Neuroreport. 1996 Jul 29;7(11):1819-23.
[90]Patel VB,Robbins M A,Topol E J. C- Reactive Protein :a“golden marker”for inflammation and coronary artery disease.Cleve Clin J Med,2001,68(6):521.
[91]Weiss SJ.Comment in.Tissue destruction by neutrophils.N Engl J Med. 1989 Feb 9;320(6):365-76.
[92]Wmi - dms JK, Sukhova GK, Herrington DM, et a1. Pravastatin has cholesterol lowering independent effects on the artery wall of atherosclerotic monkeys. Am J Coil Cardio1 1998; 31: 684 - 691.
[93]VanDer M IM.DeM aat MP. Hak AE.et a1. C- reactive protein predicts progression of atherosclerosis measuredal. rarious sites in the arterial tree: the Rotterdam study.Stroke 2002; 33: 2750.
[94]Pepys MB, Berger A.The renaissance of C - reactive protein.J. BMJ. 2001; 322: 4-5.
[95]Arturo Garcia-Touchard, Timothy D. Henry, Giuseppe Sangiorgi, et al. Extracellular Proteases in Atherosclerosis and Restenosis. Arteriosclerosis, Thrombosis, and Vascular Biology 2005; 25: 1119.
[96]Jones DA, Newham DJ, Round JM, et al.Experimental human muscle damage: morphological changes in relation to other indices of damage.J Physiol. 1986 Jun;375:435-48.
[97]Eckes B, Zigrino P, Kessler D, et al.Fibroblast-matrix interactions in wound healing and fibrosis.Matrix Biol. 2000 Aug;19(4):325-32.
[98]Gabbiani G. The myofibroblast in wound healing and fibro-contractive diseases.J Pathol.2003,200:500-503.
[99]Date M, Matsuzaki K, Matsushita M, et al.Differential regulation of activin A for hepatocyte growth and fibronectin synthesis in rat liver injury. J Hepatol. 2000 Fb;32(2):251-60.
[100]Ohga E, Matsuse T, Teramoto S, et al. Effects of activin A on proliferation and differentiation of human lung fibroblasts. Biochem Biophys Res Commun. 1996 Nov 12;228(2):391-6.
[101] Yan Y, Wanshun L, Baogin H, et al. The antioxidative and immunostimulating properties of D-glucosamine. Int Immunopharmacol, 2007; 7(1): 29-35.
[102]Zhou J, Tai G, Liu H, et al. Activin A down-regulates the phagocytosis of lipopolysaccharide-activated mouse peritoneal macrophages in vitro and in vivo. Cell Immunol 2009; 255(1-2): 69-75.
[103]Chen YG, Lui HM, Lin SL, et al.Regulation of cell proliferation, apoptosis, and carcinogenesis by activin.Exp Biol Med (Maywood). 2002 Feb;227(2):75-87.
[104]Welt C, Sidis Y, Keutmann H, et al. Activins, inhibins, and follistatins: from endocrinology to signaling. A paradigm for the new millennium.Exp Biol Med (Maywood). 2002 Oct;227(9):724-52.
[105] Wang SY, Tai GX, Zhang PY, Mu DP, Zhang XJ, Liu ZH. Inhibitory effect of activin A on activation of lipopolysaccharide-stimulated mouse macrophage RAW264.7 cells. Cytokine 2008; 42(1): 85-89.
[106] Murakamia Y, Shojia M, Hanazawab S, et al. Preventive effect of bis-eugenol, a eugenol ortho dimer on lipopolysaccharide- stimulated nuclear factor kappa B activation and inflammatory cytokine expression in macrophages. Biochem Pharmacol, 2003, 66(6): 1061–1066.
[107] Garrido G, Delgado R, Lemus Y, et al. Protection against septic shock and suppression of tumor necrosis factor alpha and nitric oxide production on macrophages and microglia by a standard aqueousextract of Mangifera indica L. (VIMANG). Role of mangiferin isolated from the extract. Pharmacological Research, 2004, 50(2): 165–172.