PDF下载 ( 1201 KB)
Recent advances in understanding microRNAs involvement in liver fibrosis
-
摘要:
肝纤维化是肝脏慢性损伤的结果。大多数慢性肝病共有的特征是细胞外基质蛋白的沉积和纤维形成,这些共同特征由复杂的信号通路网络控制。肝星形细胞和Kupffer细胞等炎症细胞参与了慢性肝脏疾病的发展。严重的肝纤维化导致肝硬化、肝功能丧失以及门静脉高压,最终必须进行肝移植才能治疗。microRNAs(miRNAs,miR)作为一类细胞内分子,被证实在肝脏纤维化发生发展过程中起着重要的调控作用,本文就miRNAs与肝脏纤维化发生发展的关系以及几种常见慢性肝脏疾病潜在的治疗新策略进行综述。
Abstract:A primary complication of chronic liver disease is liver fibrosis, yet the pathogenic mechanisms of this condition remain to be fully elucidated and may hold the key to development of effective treatment or preventive measures.Biological studies have revealed that fibrosis forms upon the aberrant deposition of extracellular matrix proteins, and molecular studies are beginning to uncover the complex signaling networks that regulate the fibrogenic process.Most recently, investigations have implicated roles for the class of small non-coding RNA molecules, microRNAs (miRNAs) , that can modulate a diverse array of physiological processes by disrupting or inhibiting gene expression at the post-translational level.In this review, we summarize the current knowledge of miRNAs in development and progression of liver fibrosis, with particular focus on the specific pathogeneses related to conditions of non-alcoholic fatty liver and viral hepatitis.In addition, the potential role of miRNAs as therapeutic targets for chronic liver diseases is discussed.
-
Key words:
- microRNAs /
- liver cirrhosis /
- fatty liver /
- hepatitis
-
[1] Lee RC, Feinbaum RL, Ambros V.The C elegans heterochronicgene lin-4 encodes small RNAs with antisense complementarity tolin-14[J].Cell, 1993, 75 (5) :843-854. [2]Nilsen TW.Mechanisms of microRNA-mediated gene regulation in ani-mal cells[J].Trends Genet, 2007, 23 (5) :243-249. [3]Lewis BP, Burge CB, Bartel DP.Conserved seed pairing, often flankedby adenosines, indicates that thousands of human genes are microRNAtargets[J].Cell, 2005, 120 (1) :15-20. [4]Calin GA, Croce CM.MicroRNA signatures in human cancers[J].Nat Rev Cancer, 2006, 6 (11) :857-866. [5] Sayed D, Abdellatif M.MicroRNAs in development and disease[J].Physiol Rev, 2011, 91 (3) :827-887. [6]Cao CY, Sun FL.MicroRNAs and tumor[J].Chin Med Herald, 2012, 9 (14) :12-14. (in Chinese) 曹长运, 孙凤林.MicroRNA和肿瘤[J].中国医药导报, 2012, 9 (14) :12-14. [7]Wang L, Xu Y.MicroRNAs-the important participant in oncogen-esis[J].Chin Med Herald, 2012, 9 (6) :15-17. (in Chinese) 王玲, 徐艳.MicroRNAs (miRNAs) -肿瘤形成过程中的重要参与者[J].中国医药导报, 2012, 9 (6) :15-17. [8]Friedman SL.Mechanisms of hepatic fibrogenesis[J].Gastroenter-ology, 2008, 134 (6) :1655-1669. [9]Chau BN, Brenner DA.What goes up must come down:the emer-ging role of microRNA in fibrosis[J].Hepatology, 2011, 53 (1) :4-6. [10]Lorenzen JM, Haller H, Thum T.MicroRNAs as mediators andtherapeutic targets in chronic kidney disease[J].Nat Rev Nephrol, 2011, 7 (5) :286-294. [11]Van Rooji E, Olson EN.Searching for MIR-acles in cardiac fibro-sis[J].Circ Res, 2009, 104 (2) :138-140. [12]Friedman SL.Liver fibrosis–from bench to bedside[J].J Hepa-tol, 2003, 38 (Suppl 1) :38-53. [13] Bataller R, Brenner DA.Liver fibrosis[J].J Clin Invest, 2005, 115 (2) :209-218. [14]Henderson NC, Iredale JP.Liver fibrosis:cellular mechanisms of pro-gression and resolution[J].Clinical Science, 2007, 112 (5) :265-280. [15]Lee UE, Friedman SL.Mechanisms of hepatic fibrogenesis[J].BestPract Res Clin Gastroenterol, 2011, 25 (2) :195-206. [16]Bataller R, Brenner DA.Liver fibrosis[J].J Clin Invest, 2005, 115 (2) :209-218. [17]Atzori L, Poli G, Perra A.Hepatic stellate cell:A star cell in the liver[J].Int J Biochem Cell B, 2009, 41 (8-9) :1639-1642. [18]Venugopal SK, Jiang J, Kim TH, et al.Liver fibrosis causes down-regulation of miRNA-150 and miRNA-194 in hepatic stellatecells, and their overexpression causes decreased stellate cell activa-tion[J].Am J Physiol Gastrointest Liver Physiol, 2010, 298 (1) :G101-106. [19]Creighton C, Murakami Y, Toyoda H, et al.The progression of liv-er fibrosis is related with overexpression of the miR-199 and 200Families[J].PLoS ONE, 2011, 6 (1) :e16081. [20]Ogawa T, Enomoto M, Fujii H, et al.MicroRNA-221/222 upregulationindicates the activation of stellate cells and the progression of liver fibrosis[J].Gut, 2012, 61 (11) :1600-1609. [21]Cheung O, Puri P, Eicken C, et al.Nonalcoholic steatohepatitis isassociated with altered hepatic MicroRNA expression[J].Hepatolo-gy, 2008, 48 (6) :1810-1820. [22]Jin X, Ye YF, Chen S, et al.MicroRNA expression pattern in dif-ferent stages of nonalcoholic fatty liver disease[J].Digest LiverDis, 2009, 41 (4) :289-297. [23]Li S, Chen X, Zhang H, et al.Differential expression of microR-NAs in mouse liver under aberrant energy metabolic status[J].JLipid Res, 2009, 50 (9) :1756-1765. [24]Alisi A, Da Sacco L, Bruscalupi G, et al.Mirnome analysis revealsnovel molecular determinants in the pathogenesis of diet-inducednonalcoholic fatty liver disease[J].Lab Invest, 2011, 91 (2) :283-293. [25]Ji J, Zhang J, Huang G, et al.Over-expressed microRNA-27aand 27b influence fat accumulation and cell proliferation during rathepatic stellate cell activation[J].FEBS Letters, 2009, 583 (4) :759-766. [26]Dolganiuc A, Petrasek J, Kodys K, et al.MicroRNA expressionprofile in Lieber-DeCarli diet-induced alcoholic and methioninecholine deficient diet-Induced nonalcoholic steatohepatitis modelsin mice[J].Alcohol Clin Exp Res, 2009, 33 (10) :1704-1710. [27]Mengshol JA, Golden-Mason L, Rosen HR.Mechanisms of dis-ease:HCV-induced liver injury[J].Nat Clin Pract GastroenterolHepatol, 2007, 4 (11) :622-634. [28]Ura S, Honda M, Yamashita T, et al.Differential microRNA ex-pression between hepatitis B and hepatitis C leading disease progres-sion to hepatocellular carcinoma[J].Hepatology, 2009, 49 (4) :1098-1112. [29]Bala S.Emerging role of microRNAs in liver diseases[J].World JGastroenterol, 2009, 15 (45) :5633-5640. [30]Hu XL, Fan GR.Functional role of microRNAs in viral hepatitis in-fection[J].J Clin Hepatol, 2012, 28 (11) :877-880 (in Chi-nese) 胡学玲, 范公忍.microRNA在乙型、丙型肝炎中的作用[J].临床肝胆病杂志, 2012, 28 (11) :877-880. [31]Liu Y, Zhao JJ, Wang CM.Altered expression profiles of microR-NAs in a stable hepatitis B virus-expressing cell line[J].ChinMed J, 2009, 122 (1) :10-14. [32]Bandyopadhyay S, Friedman RC, Marquez RT, et al.Hepatitis Cvirus infection and hepatic stellate cell activation downregulate miR-29:miR-29 overexpression reduces hepatitis C viral abundancein culture[J].J infect Dis, 2011, 203 (12) :1753-1762. [33]Pfeffer S, Baumert TF.Unravelling the importance of microRNAsduring hepatitis C virus infection in the human liver[J].J Hepatol, 2009, 51 (3) :606-609. [34]Jopling CL, Yi M, Lancaster AM, et al.Modulation of hepatitis Cvirus RNA abundance by a liver-specific microRNA[J].Science, 2005, 309 (5740) :1577-1581. [35]Hou W, Tian Q, Zheng J, et al.MicroRNA-196 represses Bach1protein and hepatitis C virus gene expression in human hepatomacells expressing hepatitis C viral proteins[J].Hepatology, 2010, 51 (5) :1494-1504. -
本文二维码
计量
- 文章访问数: 3058
- HTML全文浏览量: 13
- PDF下载量: 690
- 被引次数: 0
下载:
