肝星状细胞的生物学特性及活化调控机制
饶慧瑛,北京大学人民医院、北京大学肝病研究所 北京市 100044
项目负责人:饶慧瑛, 100044, 北京市, 北京大学人民医院、北京大学肝病研究所. raohuiying@163.com
电话: 010-68314422-5725
收稿日期: 2004-12-31 接受日期: 2005-01-20
摘要激活的肝星状细胞(hepatic stellate cells，HSC)是肝纤维化发生发展过程中的关键环节.正常情况下HSC参与Vit A的代谢和贮存，参与细胞外基质的合成和降解，表达细胞因子及受体.肝脏损伤后，HSC发生激活.HSC的激活是多种细胞因子的旁分泌和自分泌协同作用的结果.其中PDGF以及TGF-b是两个最重要的因子.PDGF能促使HSC大量分裂增生并向肝损伤部位迁徙，TGF-b能促进HSC合成a-SMA以及合成胶原、纤维连接蛋白和蛋白多糖等细胞外基质.ET-1 的收缩功能是HSC的重要生物学特性之一.肝损伤过程中，细胞与细胞间，基质与HSC间存在多种细胞因子及非肽类递质构成的复杂HSC激活调节网络.
, http://www.100md.com
饶慧瑛, 魏来. 肝星状细胞的生物学特性及活化调控机制. 世界华人消化杂志 2005;13(5):671-6741 Geerts A. History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells.
Semin Liver Dis 2001;21:311-335
2 Wake K. "Sternzellen" in the liver:perisinusoidal cells with special reference to storage of vitamin A.
Am J Anat 1971;132:429-462
3 Ahern M, Hall P, Halliday J. Hepatic stellate cells nomenclature(letter). Hepatology 1996;23:193
, 百拇医药
4 Wake K. Perisinusoidal Stellate cells(fat-storing cells interstitial cells, Lipocytes), their related structure in and around
the liver sinusoids, and vitamin A-storing cells in extrahepatic organs. Int Rev Cytol 1980;66:303-353
5 Bronfenmajer S, Schaffner F, Popper H. Fat-storing cells(lipocytes)in human liver. Arch Pathol 1966;82:447-453
6 Neubauer K, Knittel T, Aurisch S, Fellmer P, Ramadori G. Glial fibrillary acidic protein-a cell type specific marker for
, http://www.100md.com
Ito cells in vivo and in vitro. J Hepatol 1996;24:719-730
7 Niki T, De Bleser PJ, Xu G, Van Den Berg K, Wisse E, Geerts A. Comparison of glial fibrillary acidic protein and
desmin staining in normal and CCl4-induced fibrotic rat livers. Hepatology 1996;23:1538-1545
8 Iredale JP, Murphy G, Hembry RM, Friedman SL, Arthur MJ. Human hepatic lipocytes synthesize tissue inhibitor of
, 百拇医药
metalloproteinases-1. Implications for regulation of matrix degradation in liver. J Clin Invest 1992;90:282-287
9 Pinzani M, Marra F, Carloni V. Signal transduction in hepatic stellate cells. Liver 1998;18:2-13
10 Faouzi S, Le Bail B, Neaud V, Boussarie L, Saric J, Bioulac-Sage P, Balabaud C, Rosenbaum J. Myofibroblasts are
responsible for collagen synthesis in the stroma of human hepatocellular carcinoma:an in vivo and in vitro study.
, 百拇医药
J Hepatol 1999;30:275-284
11 Ballardini G, Groff P, Badiai de Giorgi L, Schuppan D, Bianchi FB. Ito cell heterogeneity:desmin-negative Ito cells in
normal rat liver. Hepatology 1994;19:440-446
12 Nagy NE, Holven KB, Roos N, Senoo H, Kojima N, Norum KR, Blomhoff R. Storage of vitamin A in extrahepatic stellate
cells in normal rats. J Lipid Res 1997;38:645-658
, 百拇医药
13 Zou Z, Ekataksin W, Wake K. Zonal and regional differences identified from precision mapping of vitamin A-storing
lipid droplets of the hepatic stellate cells in pig liver:a novel concept of addressing the intralobular area of
heterogeneity. Hepatology 1998;27:1098-1108
14 Friedman SL, Arthur MJ. Activatin of cultured rat hepatic lipocytes by Kupffer cell conditioned medium. Direct
, 百拇医药
enhancement of matrix synthesis and stimulation of cell proliferation via induction of platelet-derived growth factor
receptors. J Clin Invest 1989;84:1780-1785
15 Davis BH, Coll D, Beno DW. Retinoic acid suppresses the response to platelet-derived growth factor in human
hepatic Ito-cell-like myofibroblasts:a post-receptor mechanism independent of raf/fos/jun/egr activation.
, 百拇医药
Biochem J 1993;294:785-791
16 Nakamura T, Sakata R, Ueno T, Sata M, Ueno H. Inhibition of transforming growth factor beta prevents progression
of liver fibrosis and enhances hepatocyte regeneration in dimethylnitrosamine-treated rats. Hepatology
2000;32:247-255
17 Pinzani M, Marra F. Cytokine receptors and signaling in hepatic stellate cells. Semin Liver Dis 2001;21:397-416
, 百拇医药
18 Sanderson N, Factor V, Nagy P, Kopp J, Kondaiah P, Wakefield L, Roberts AB, Sporn MB, Thorgeirsson SS. Hepatic
expression of mature transforming growth factor b1 in transgenic mice results in multiple tissue lesions.
Proc Natl Acad Sci USA 1995;92:2572-2576
19 Stopa M, Benes V, Ansorge W, Gressner AM, Dooley S. Genomic locus and promoter region of rat Smad7, an
, 百拇医药
important antagonist of TGFbeta signaling. Mamm Genome 2000;11:169-176
20 Thimgan MS, Yee HF Jr. Quantitation of rat hepatic stellate cell contraction:stellate cells contribution to sinusoidal
resistance. Am J Physiol 1999;277(1 Pt 1):G137-143
21 Gupta TK, Toruner M, Chung MK, Groszmann RJ. Endothelial dysfunction and decreased production of nitric oxide in
, 百拇医药
the intrahepatic micocirculation of cirrhotic rats. Hepatology 1998;28:926-931
22 Goto T, Mikami KI, Miura K, Ohshima S, Yoneyama K, Nakane K, Watanabe D, Otaka M, Watanabe S. Mechanical
stretch induces matrix metalloproteinase 1 production in human hepatic stellate cells. Pathophysiology 2004;11:153-158
编辑 张海宁, 百拇医药( 饶慧瑛,魏 来)
项目负责人:饶慧瑛, 100044, 北京市, 北京大学人民医院、北京大学肝病研究所. raohuiying@163.com
电话: 010-68314422-5725
收稿日期: 2004-12-31 接受日期: 2005-01-20
摘要激活的肝星状细胞(hepatic stellate cells，HSC)是肝纤维化发生发展过程中的关键环节.正常情况下HSC参与Vit A的代谢和贮存，参与细胞外基质的合成和降解，表达细胞因子及受体.肝脏损伤后，HSC发生激活.HSC的激活是多种细胞因子的旁分泌和自分泌协同作用的结果.其中PDGF以及TGF-b是两个最重要的因子.PDGF能促使HSC大量分裂增生并向肝损伤部位迁徙，TGF-b能促进HSC合成a-SMA以及合成胶原、纤维连接蛋白和蛋白多糖等细胞外基质.ET-1 的收缩功能是HSC的重要生物学特性之一.肝损伤过程中，细胞与细胞间，基质与HSC间存在多种细胞因子及非肽类递质构成的复杂HSC激活调节网络.
, http://www.100md.com
饶慧瑛, 魏来. 肝星状细胞的生物学特性及活化调控机制. 世界华人消化杂志 2005;13(5):671-6741 Geerts A. History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells.
Semin Liver Dis 2001;21:311-335
2 Wake K. "Sternzellen" in the liver:perisinusoidal cells with special reference to storage of vitamin A.
Am J Anat 1971;132:429-462
3 Ahern M, Hall P, Halliday J. Hepatic stellate cells nomenclature(letter). Hepatology 1996;23:193
, 百拇医药
4 Wake K. Perisinusoidal Stellate cells(fat-storing cells interstitial cells, Lipocytes), their related structure in and around
the liver sinusoids, and vitamin A-storing cells in extrahepatic organs. Int Rev Cytol 1980;66:303-353
5 Bronfenmajer S, Schaffner F, Popper H. Fat-storing cells(lipocytes)in human liver. Arch Pathol 1966;82:447-453
6 Neubauer K, Knittel T, Aurisch S, Fellmer P, Ramadori G. Glial fibrillary acidic protein-a cell type specific marker for
, http://www.100md.com
Ito cells in vivo and in vitro. J Hepatol 1996;24:719-730
7 Niki T, De Bleser PJ, Xu G, Van Den Berg K, Wisse E, Geerts A. Comparison of glial fibrillary acidic protein and
desmin staining in normal and CCl4-induced fibrotic rat livers. Hepatology 1996;23:1538-1545
8 Iredale JP, Murphy G, Hembry RM, Friedman SL, Arthur MJ. Human hepatic lipocytes synthesize tissue inhibitor of
, 百拇医药
metalloproteinases-1. Implications for regulation of matrix degradation in liver. J Clin Invest 1992;90:282-287
9 Pinzani M, Marra F, Carloni V. Signal transduction in hepatic stellate cells. Liver 1998;18:2-13
10 Faouzi S, Le Bail B, Neaud V, Boussarie L, Saric J, Bioulac-Sage P, Balabaud C, Rosenbaum J. Myofibroblasts are
responsible for collagen synthesis in the stroma of human hepatocellular carcinoma:an in vivo and in vitro study.
, 百拇医药
J Hepatol 1999;30:275-284
11 Ballardini G, Groff P, Badiai de Giorgi L, Schuppan D, Bianchi FB. Ito cell heterogeneity:desmin-negative Ito cells in
normal rat liver. Hepatology 1994;19:440-446
12 Nagy NE, Holven KB, Roos N, Senoo H, Kojima N, Norum KR, Blomhoff R. Storage of vitamin A in extrahepatic stellate
cells in normal rats. J Lipid Res 1997;38:645-658
, 百拇医药
13 Zou Z, Ekataksin W, Wake K. Zonal and regional differences identified from precision mapping of vitamin A-storing
lipid droplets of the hepatic stellate cells in pig liver:a novel concept of addressing the intralobular area of
heterogeneity. Hepatology 1998;27:1098-1108
14 Friedman SL, Arthur MJ. Activatin of cultured rat hepatic lipocytes by Kupffer cell conditioned medium. Direct
, 百拇医药
enhancement of matrix synthesis and stimulation of cell proliferation via induction of platelet-derived growth factor
receptors. J Clin Invest 1989;84:1780-1785
15 Davis BH, Coll D, Beno DW. Retinoic acid suppresses the response to platelet-derived growth factor in human
hepatic Ito-cell-like myofibroblasts:a post-receptor mechanism independent of raf/fos/jun/egr activation.
, 百拇医药
Biochem J 1993;294:785-791
16 Nakamura T, Sakata R, Ueno T, Sata M, Ueno H. Inhibition of transforming growth factor beta prevents progression
of liver fibrosis and enhances hepatocyte regeneration in dimethylnitrosamine-treated rats. Hepatology
2000;32:247-255
17 Pinzani M, Marra F. Cytokine receptors and signaling in hepatic stellate cells. Semin Liver Dis 2001;21:397-416
, 百拇医药
18 Sanderson N, Factor V, Nagy P, Kopp J, Kondaiah P, Wakefield L, Roberts AB, Sporn MB, Thorgeirsson SS. Hepatic
expression of mature transforming growth factor b1 in transgenic mice results in multiple tissue lesions.
Proc Natl Acad Sci USA 1995;92:2572-2576
19 Stopa M, Benes V, Ansorge W, Gressner AM, Dooley S. Genomic locus and promoter region of rat Smad7, an
, 百拇医药
important antagonist of TGFbeta signaling. Mamm Genome 2000;11:169-176
20 Thimgan MS, Yee HF Jr. Quantitation of rat hepatic stellate cell contraction:stellate cells contribution to sinusoidal
resistance. Am J Physiol 1999;277(1 Pt 1):G137-143
21 Gupta TK, Toruner M, Chung MK, Groszmann RJ. Endothelial dysfunction and decreased production of nitric oxide in
, 百拇医药
the intrahepatic micocirculation of cirrhotic rats. Hepatology 1998;28:926-931
22 Goto T, Mikami KI, Miura K, Ohshima S, Yoneyama K, Nakane K, Watanabe D, Otaka M, Watanabe S. Mechanical
stretch induces matrix metalloproteinase 1 production in human hepatic stellate cells. Pathophysiology 2004;11:153-158
编辑 张海宁, 百拇医药( 饶慧瑛,魏 来)
