RhoA在肝纤维化中的作用机制

洪金妮; 安海燕

doi:10.3969/j.issn.1001-5256.2013.08.023

RhoA在肝纤维化中的作用机制

DOI: 10.3969/j.issn.1001-5256.2013.08.023

南方医科大学中医药学院

基金项目:

广东省中医药局2011年立项课题(20111272)；国家级大学生创新创业训练计划项目(201212121053)；

详细信息

中图分类号: R575.2
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出版历程
- 收稿日期: 2012-12-24
- 出版日期: 2013-08-20

Research progress in role of RhoA in onset and development of hepatic fibrosis

Research funding:

摘要

摘要:
肝纤维化发生的关键在于肝星状细胞(HSC)转化为成纤维母细胞及活化后细胞外基质(ECM)的异常表达。回顾了Rho/ROCK信号通路在HSC的激活中的重要作用。总结了RhoA,作为Rho/ROCK信号通路上小G蛋白家庭成员之一,且作为一种重要的调节肌动蛋白细胞骨架和细胞形态异质性的细胞因子,参与肝纤维化的进程。指出RhoA在肝脏纤维化发生发展过程中起着重要的调控作用,归纳了RhoA通过调节肌动蛋白应力纤维的装配,并通过级联放大效应影响细胞基质的合成和收缩,最终影响肝纤维化的进展。就RhoA在肝纤维化过程中的机制以及RhoA作为潜在的治疗靶点作一综述。
- 肝硬化 /
- ρA GTP结合蛋白质 /
- rho相关激酶类
Abstract:
The key step in the pathogenesis of hepatic fibrosis is the activation of hepatic stellate cells (HSCs) into fibroblasts and the abnormal expression of extracellular matrix (ECM) after activation.The important role of Rho/ROCK signaling pathway in the activation of HSCs is reviewed.It is summarized that RhoA, a member of the small G-protein family in Rho/ROCK signaling pathway, gets involved in hepatic fibrosis as an important cytokine for regulating the actin cytoskeleton and morphological heterogeneity of cells.It is pointed out that RhoA plays an important regulatory role in the onset and development of hepatic fibrosis and that RhoA adjusts the assembly of actin stress fibers and influences the synthesis and contraction of ECM through cascade amplification.The role of RhoA in the onset and development of hepatic fibrosis and its significance as a potential therapeutic target for hepatic fibrosis are reviewed.
- liver cirrhosis /
- rhoA GTP-binding protein /
- rho-associated kinases

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参考文献(28)

[1]WANG B, WANG TC, LIANG KH.Role of cytokine RhoA in the formation of hepatic fibrosis in rats[J].Chin J Dig, 2004, 24 (7) :414-417. (in Chinese) 王波, 王天才, 梁扩寰.细胞因子RhoA在实验性大鼠肝纤维化形成过程中的作用机制[J].中华消化杂志, 2004, 24 (7) :414-417.

[2]WANG B, WANG TC, LIANG KH.Mechanisms of stress fiber, vinculin and FAK on hepatic fibrosis in rats[J].Acta Univ Med Tangji, 2004, 33 (3) :282-285. (in Chinese) 王波, 王天才, 梁扩寰.应力纤维、纽蛋白和粘着斑激酶对大鼠肝纤维化作用机制的研究[J].华中科技大学学报:医学版, 2004, 33 (3) :282-285.

[3]MELTON AC, DATTA A, YEE HJ.[Ca 2+]i-independent con-tractile force generation by rat hepatic stellate cells in response toendothelin-1[J].Am J Physiol Gastrointest Liver Physiol, 2006, 290 (1) :g7-g13.

[4]ZHANG XL, LI X, XIAO B, et al.Effect of angiotensinⅡon Rho-Rock pathway in rat hepatic stellate cell contraction[J].J South Med Univ, 2008, 28 (6) :968-971. (in Chinese) 张小兰, 李旭, 肖冰, 等.血管紧张素Ⅱ对大鼠肝星状细胞收缩及Rho-Rock通路的影响[J].南方医科大学学报, 2008, 28 (6) :968-971.

[5]LALEMAN W, van LANDEGHEM L, SEVERI T, et al.Both Ca 2+-dependent and-independent pathways are involved in rat hepat-ic stellate cell contraction and intrahepatic hyperresponsiveness to methoxamine[J].Am J Physiol Gastrointest Liver Physiol, 2007, 292 (2) :g556-g564.

[6]HEASMAN SJ, RIDLEY AJ.Mammalian Rho GTPases:new in-sights into their functions from in vivo studies[J].Nat Rev Mol Cell Biol, 2008, 9 (9) :690-701.

[7]AMANO M, CHIHARA K, NAKAMURA N, et al.The COOH ter-minus of Rho-kinase negatively regulates rho-kinase activity[J].J Biol Chem, 1999, 274 (45) :32418-32424.

[8]WANG B, WANG YF, TIAN DA, et al.Inhibition of RhoA ex-pression reduces the secretion of extracellular matrix components in hepatic stellate cells[J].World Chin J Dig, 2010, 18 (19) :2038-2042. (in Chinese) 王波, 王艳芬, 田德安, 等.抑制细胞因子RhoA的表达对肝星状细胞株HSC-T6胶原分泌的影响[J].世界华人消化杂志, 2010, 18 (19) :2038-2042.

[9]HENNENBERG M, BIECKER E, TREBICKA J, et al.Defective RhoA/Rho-kinase signaling contributes to vascular hypocontractility and vasodilation in cirrhotic rats[J].Gastroenterology, 2006, 130 (3) :838-854.

[10]WANG B, WANG TC, TIAN DA.Molecular mechanism of the effect of Y27632, an antagonist of ROCK, depressing liver fibrosis[J].Chin J Gastroenterol Hepatol, 2010, 19 (9) :787-790. (in Chinese) 王波, 王天才, 田德安.ROCK阻断剂Y27632干预大鼠实验性肝纤维化的分子机制研究[J].胃肠病学和肝病学杂志, 2010, 19 (9) :787-790.

[11]JI H, MENG Y, ZHANG X, et al.Aldosterone induction of hepatic stel-late cell contraction through activation of RhoA/ROCK-2signaling path-way[J].Regul Pept, 2011, 169 (1-3) :13-20.

[12]XU H, ZHOU Y, LU C, et al.Salvianolic acid B lowers portal pressure in cirrhotic rats and attenuates contraction of rat hepatic stellate cells by inhibiting RhoA signaling pathway[J].Lab Invest, 2012, 92 (12) :1738-1748.

[13]TOX U, STEFFEN HM.Impact of inhibitors of the Renin-Angioten-sin-aldosterone system on liver fibrosis and portal hypertension[J].Curr Med Chem, 2006, 13 (30) :3649-3661.

[14]KITAMURA K, TADA S, NAKAMOTO N, et al.Rho/Rho kinase is a key enzyme system involved in the angiotensin II signaling path-way of liver fibrosis and steatosis[J].J Gastroenterol Hepatol, 2007, 22 (11) :2022-2033.

[15]MAO YA, LIANG XM, FU HY, et al.Effects ofβ-elemene onα-tubulin of Human Hepatocarcinoma HepG-2Cells[J].China Cancer, 2012, 21 (2) :145-149. (in Chinese) 毛雨秋, 梁鑫淼, 付海雁, 等.β-榄香烯注射液对人肝癌HepG-2细胞微管蛋白α的影响[J].中国肿瘤, 2012, 21 (2) :145-149.

[16]MURPHY GA, SOLSKI PA, JILLIAN SA, et al.Cellular functions of TC10, a Rho family GTPase:regulation of morphology, signal transduction and cell growth[J].Oncogene, 1999, 18 (26) :3831-3845.

[17]RIDLEY AJ.Rho GTPases and cell migration[J].J Cell Sci, 2001, 114 (15) :2713-2722.

[18]ZHOU W, YANG L, HU SJ, Rho proteins and hepatic stellate cells[J].World Chin J Dig, 2009, 17 (24) :2469-2473. (in Chi-nese) 周雯, 杨玲, 胡胜军.Rho蛋白与肝星状细胞[J].世界华人消化杂志, 2009, 17 (24) :2469-2473.

[19]WANG YZ, JIANG HQ, HU CX, et al.Expressions of RhoA and phosphorylated myosin light chain in rat liver tissue undergoing he-patic fibrogenesis[J].Basic Med Sci Clin, 2007, 27 (3) :275-278. (in Chinese) 王玉珍, 姜慧卿, 扈彩霞, 等.RhoA和肌球蛋白轻链在肝纤维化大鼠肝组织中的表达[J].基础医学与临床, 2007, 27 (3) :275-278.

[20]FENG Y.Inhibition role of Y-27632on myosin phosphatase in rat he-patic stellate cells[D].Hebei Med Univ, 2007. (in Chinese) 冯岩.Y-27632对大鼠肝星状细胞肌球蛋白磷酸酶抑制作用的实验研究[D].河北医科大学, 2007.

[21]LI L.Study on the role and mechanisms of hepatic stellate cells mi-gration and RhoA signaling transduction pathway in liver fibrosis[D].Fudan Univ, 2006. (in Chinese) 李蕾.肝纤维化中肝星状细胞迁移及RhoA作用机制的研究[D].复旦大学, 2006.

[22]HAMEL B, MONAGHAN-BENSON E, ROJAS RJ, et al.Smg-GDS is a guanine nucleotide exchange factor that specifically acti-vates RhoA and RhoC[J].J Biol Chem, 2011, 286 (14) :12141-12148.

[23]LI F, GAO HC, SHENG XT, et al.Effect of sodium ferulate on Rho/Rock Signal pathway and its protective effect on liver tissue[J].J Jilin Univ:Med Edit, 2012, 38 (5) :889-893. (in Chi-nese) 李凤, 高海成, 盛晓彤, 等.阿魏酸钠干预对Rho/Rock信号通路的影响及其对肝脏的保护作用[J].吉林大学学报:医学版, 2012, 38 (5) :889-893.

[24]LI L, LI J, WANG JY, et al.Role of RhoA in platelet-derived growth factor-BB-induced migration of rat hepatic stellate cells[J].Chin Med J (Engl) , 2010, 123 (18) :2502-2509.

[25]CHOI SS, SYN WK, KARACA GF, et al.Leptin promotes the myofibroblastic phenotype in hepatic stellate cells by activating the hedgehog pathway[J].J Biol Chem, 2010, 285 (47) :36551-36560.

[26]ZHAO ZB, LI JF, HUANG SS, et al.The advances of profibrogen-ic research of leptin and its signaling pathways in hepatic fibrosis[J].J Clin Hepatol, 2011, 27 (10) :1106-1108. (in Chinese) 赵正斌, 李俊峰, 黄双盛, 等.瘦素及其信号通路促肝纤维化机制研究进展[J].临床肝胆病杂志, 2011, 27 (10) :1106-1108.

[27] SHI YY, SHEN FJ, YANG F.Effect of Benazepril on ACE2and Ang- (1-7) of hepatic fibrosis in rats[J].J Clin Hepatol, 2011, 27 (3) :258-260. (in Chinese) 史媛媛, 申凤俊, 杨芳.贝那普利对肝纤维化大鼠ACE2和Ang- (1-7) 的影响[J].临床肝胆病杂志, 2011, 27 (3) :258-260.

[28]HUANG ML.Effects of the ACE2-Ang- (1-7) -Mas Axis on Colla-gen Synthesis in Hepatic Stellate Cells and Its Signal Transduction Mecha-nism[D].Southern Med Univ, 2010 (in Chinese) 黄茂梁.ACE2-Ang- (1-7) -Mas轴对肝星状细胞胶原合成的影响及其信号转导机制研究[D].南方医科大学, 2010.

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