microRNA在肝纤维化进程中的作用

李彬彬; 明健; 陈大贵; 许蜜蝶; 颜红柱; 朱樑; 余宏宇

microRNA在肝纤维化进程中的作用

第二军医大学长征医院病理科

基金项目:

上海市科委基金(10142201000)；国家自然科学基金(30870976)；

详细信息

中图分类号: R575.2
计量
- 文章访问数: 3298
- HTML全文浏览量: 21
- PDF下载量: 784
- 被引次数: 0
出版历程
- 出版日期: 2013-05-20

Recent progress in understanding the role of microRNAs in hepatic stellate cell biology and liver fibrosis pathogenesis

Research funding:

摘要

摘要:
微小RNA(microRNA,miRNA)是一类长约21～22nt的内源性非编码调控RNA,可作用于靶mRNA导致其降解或抑制其翻译,对基因表达起重要的负性调控作用,参与体内如发育、细胞分化、细胞增殖、细胞死亡等众多重要的生物学进程。近年研究发现,miRNA这一转录后水平调控分子在肝纤维化发生发展中起着重要的作用。已发现若干miRNA可调控参与肝纤维化形成的细胞因子或通过调控肝星状细胞(HSC)的活化增殖、凋亡等,促进或减缓纤维化进程,本文对miRNA在HSC及肝纤维化进程中的研究进展作一综述。
- 微RNAs /
- 肝硬化 /
- 脂细胞
Abstract:
Small non-coding RNAs (2122nt in length;known as microRNAs, miRNAs) regulate a broad array of biological processes by disrupting gene expression through physically degrading or inhibiting translation of target mRNA sequences.miRNA-mediated regulation of gene expression has been demonstrated in both physiologic and pathogenic processes of cellular differentiation, proliferation, and death.Recent studies of liver fibrosis have begun to implicate miRNAs in the disease development and progression, which in turn suggests a potential new perspective for preventive and therapeutic molecular strategies.In this review, we summarize the various miRNAs identified as differentially expressed under conditions of liver fibrosis and then detail the latest findings regarding their roles in activation of hepatic stellate cells (HSCs) , the key early event in liver fibrosis.In addition, the latest findings regarding which signaling pathways and factors (such as cytokines, growth and apoptotic factors) these miRNAs interact with and modulate are discussed to provide a comprehensive insight into the fibrosis-related functions of miRNAs which may be manipulated to reduce, halt, or reverse the fibrotic process.
- microRNAs /
- liver cirrhosis /
- adipocytes

HTML全文

参考文献(36)

[1]Fan XQ, Chen XH, Qi XY.Research progress on targeted connectivetissue growth factor of siRNA for hepatic stellate cell mediated liver fi-brosis[J].Chin Med Herald, 2012, 9 (35) :58-60. (in Chinese) 樊雪强, 陈新华, 齐晓艳.靶向结缔组织生长因子的siRNA对于肝星状细胞介导肝纤维化的研究进展[J].中国医药导报, 2012, 9 (35) :58-60.

[2]Cai FS.Clinical efficacy of Dahuang Zhechong pills combined with lami-vudine in treatment of hepatic fibrosis in chronic hepatis B[J].J Chang-chun Uni Tradit Chin Med, 2011, 27 (6) :1007-1008.蔡丰穗.大黄蟅虫丸联合拉米夫定治疗慢性乙型肝炎肝纤维化临床观察[J].长春中医药大学学报, 2011, 27 (6) :1007-1008.

[3]Haybaeck J, Zeller N, Heikenwalder M.The parallel universe:microR-NAs and their role in chronic hepatitis, liver tissue damage and hepato-carcinogenesis[J].Swiss Med Wkly, 2011, 141:w13287.

[4]Noetel A, Kwiecinski M, Elfimova N, et al.microRNA are centralplayers in anti-and profibrotic gene regulation during liver fibrosis[J].Front Physiol, 2012, 3:49.

[5]Guo CJ, Pan Q, Cheng T, et al.Changes in microRNAs associatedwith hepatic stellate cell activation status identify signaling pathways[J].FEBS J, 2009, 276 (18) :5163-5176.

[6]Murakami Y, Toyoda H, Tanaka M, et al.The progression of liverfibrosis is related with overexpression of the miR-199 and 200 fam-ilies[J].PLoS One, 2011, 6 (1) :e16081.

[7]Chen C, Wu CQ, Zhang ZQ, et al.Loss of expression of miR-335is implicated in hepatic stellate cell migration and activation[J].Experimental Cell Research, 2011, 317 (12) :1714-1725.

[8]Lakner AM, Steuerwald NM, Walling TL, et al.Inhibitory effectsof microRNA 19b in hepatic stellate cell-mediated fibrogenesis[J].Hepatology, 2012, 56 (1) :300-310.

[9]Wang B, Li W, Guo K, et al.miR-181b Promotes hepatic stellatecells proliferation by targeting p27 and is elevated in the serum ofcirrhosis patients[J].Biochem Biophys Res Commun, 2012, 421 (1) :4-8.

[10]Sekiya Y, Ogawa T, Yoshizato K, et al.Suppression of hepaticstellate cell activation by microRNA-29b[J].Biochem BiophysRes Commun, 2011, 412 (1) :74-79.

[11]Kwiecinski M, Elfimova N, Noetel AT, et al.Expression of platelet-derived growth factor-C and insulin-like growth factor I in he-patic stellate cells is inhibited by miR-29[J].Lab Invest, 2012, 92 (7) :978-987.

[12]Kwiecinski M, Noetel A, Elfimova N, et al.Hepatocyte growth factor (HGF) inhibits collagen I and IV synthesis in hepatic stellate cells bymiRNA-29 induction[J].PLoS One, 2011, 6 (9) :e24568.

[13]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.

[14]Guo CJ, Pan Q, Li DG, et al.miR-15b and miR-16 are impli-cated in activation of the rat hepatic stellate cell:An essential rolefor apoptosis[J].J Hepatol, 2009, 50 (4) :766-778.

[15]Guo CJ, Pan Q, Jiang B, et al.Effects of upregulated expression ofmicroRNA-16 on biological properties of culture-activated hepat-ic stellate cells[J].Apoptosis, 2009, 14 (11) :1331-1340.

[16]Li WQ, Chen C, Xu MD, et al.The rno-miR-34 family is up-regulated and targets ACSL1 in dimethylnitrosamine-induced he-patic fibrosis in rats[J].FEBS J, 2011, 278 (9) :1522-1532.

[17]Ogawa T, Enomoto M, Fujii H, et al.MicroRNA-221/222 upreg-ulation indicates the activation of stellate cells and the progression ofliver fibrosis[J].Gut, 2012, 61 (11) :1600-1609.

[18]He Y, Huang C, Sun X, et al.MicroRNA-146a modulates TGF-beta1-induced hepatic stellate cell proliferation by targetingSMAD4[J].Cell Signal, 2012, 24 (10) :1923-1930.

[19]Huebert RC, Jagavelu K, Hendrickson HI, et al.Aquaporin-1promotes angiogenesis, fibrosis, and portal hypertension throughmechanisms dependent on osmotically sensitive microRNAs[J].Am J Pathol, 2011, 179 (4) :1851-1860.

[20]Jiang A, Zhang S, Li Z, et al.miR-615-3p promotes the phago-cytic capacity of splenic macrophages by targeting ligand-depend-ent nuclear receptor corepressor in cirrhosis-related portal hyper-tension[J].Exp Biol Med (Maywood) , 2011, 236 (6) :672-680.

[21]Gui J, Tian Y, Wen X, et al.Serum microRNA characterizationidentifiesmiR-885-5pas a potential marker for detecting liver pa-thologies[J].Clinical Science, 2011, 120 (5) :183-193.

[22]Yoshida K, Matsuzaki K.Differential regulation of TGF-beta/Smad signaling in hepatic stellate cells between acute and chronicliver injuries[J].Front Physiol, 2012, 3:53.

[23]Fang Y, Yu S, Braley-Mullen H.TGF-beta promotes prolifera-tion of thyroid epithelial cells in IFN-gamma (-/-) mice bydown-regulation of p21 and p27 via AKT pathway[J].Am JPathol, 2012, 180 (2) :650-660.

[24]El-Karef A, Yoshida T, Gabazza EC, et al.Deficiency of tenascin-C attenuates liver fibrosis in immune-mediated chronic hepatitis inmice[J].J Pathol, 2007, 211 (1) :86-94.

[25]Bonner JC.Regulation of PDGF and its receptors in fibrotic diseases[J].Cytokine Growth Factor Rev, 2004, 15 (4) :255-273.

[26]Sobrevals L, Rodriguez C, Romero-Trevejo JL, et al.Insulin-like growth factor I gene transfer to cirrhotic liver induces fibrolysisand reduces fibrogenesis leading to cirrhosis reversion in rats[J].Hepatology, 2010, 51 (3) :912-921.

[27]Wu YL, Wan Y, Jin XJ, et al.25-OCH3-PPD induces the ap-optosis of activated t-HSC/Cl-6 cells via c-FLIP-mediated NF-kappaB activation[J].Chem Biol Interact, 2011, 194 (2-3) :106-112.

[28]Novo E, Marra F, Zamara E, et al.Overexpression of Bcl-2 byactivated human hepatic stellate cells:resistance to apoptosis as amechanism of progressive hepatic fibrogenesis in humans[J].Gut, 2006, 55 (8) :1174-1182.

[29]Leist M, Jaattela M.Four deaths and a funeral:from caspases to alter-native mechanisms[J].Nat Rev Mol Cell Biol, 2001, 2 (8) :589-598.

[30]Ramani K, Tomasi ML.Transcriptional regulation of methionine ad-enosyltransferase 2A by peroxisome proliferator-activated receptorsin rat hepatic stellate cells[J].Hepatology, 2012, 55 (6) :1942-1953.

[31] Galli A, Crabb D, Price D, et al.Peroxisome proliferator-activa-ted receptor gamma transcriptional regulation is involved in platelet-derived growth factor-induced proliferation of human hepaticstellate cells[J].Hepatology, 2000, 31 (1) :101-108.

[32]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 Lett, 2009, 583 (4) :759-766.

[33]Kida K, Nakajima M, Mohri T, et al.PPARalpha is regulated bymiR-21 and miR-27b in human liver[J].Pharm Res 2011, 28 (10) :2467-2476.

[34]Yang MD, Chiang YM, Higashiyama R, et al.Rosmarinic acid and ba-icalin epigenetically derepress peroxisomal proliferator-activated recep-tor gamma in hepatic stellate cells for their antifibrotic effect[J].Hepa-tology, 2012, 55 (4) :1271-1281.

[35]Mann J, Chu DC, Maxwell A, et al.MeCP2 controls an epigeneticpathway that promotes myofibroblast transdifferentiation and fibrosis[J].Gastroenterology, 2010, 138 (2) :705-714, 714.e701-704.

[36]Hu XL, Fan GR.Functional role of microRNAs in viral hepatitis in-fections[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.

施引文献

资源附件(0)

访问统计