School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natrual Products, Anhui Medical University, Hefei 230032, China.
Cell Signal. 2012 Dec;24(12):2268-72. doi: 10.1016/j.cellsig.2012.07.023. Epub 2012 Aug 3.
MicroRNAs (miRNAs) are a class of ~22-nucleotides noncoding RNAs that regulate gene expression by specifically binding with 3'-untranslated region (3'-UTR) of target gene mRNAs to posttranscriptionally effect mRNA stability and translation,and play essential roles in a variety of biological processes, including cell development, proliferation, differentiation, and apoptosis. Liver fibrosis is the occurrence of liver cell necrosis and inflammatory stimulation, and is characterized by excessive accumulation of extracellular matrices(ECMs). In the fibrotic liver, hepatic stellate cells (HSCs), which are regulated by multiple signal transduction pathways, undergo myofibroblastic transdifferentiation and are generally regarded as the major ECM producer responsible for liver fibrosis. A growing body of evidence suggests that divergent miRNAs participate in liver fibrotic process and activation of HSC. Moreover, members of many signal transduction pathways are important targets for miRNAs. In this review, we make a summary on current understanding of the roles of miRNAs in the development of liver fibrosis, HSC functions and their potential as novel drug targets.
微小 RNA(miRNAs)是一类约 22 个核苷酸的非编码 RNA,通过特异性结合靶基因 mRNAs 的 3'-非翻译区(3'-UTR)来调节基因表达,从而在后转录水平上影响 mRNA 的稳定性和翻译,在包括细胞发育、增殖、分化和凋亡在内的多种生物学过程中发挥重要作用。肝纤维化是肝细胞坏死和炎症刺激的发生,其特征是细胞外基质(ECM)的过度积累。在纤维化的肝脏中,受多种信号转导途径调控的肝星状细胞(HSCs)经历肌成纤维细胞的转分化,通常被认为是导致肝纤维化的主要 ECM 产生细胞。越来越多的证据表明,不同的 miRNAs 参与肝纤维化过程和 HSC 的激活。此外,许多信号转导途径的成员是 miRNAs 的重要靶点。在这篇综述中,我们总结了 miRNAs 在肝纤维化发展、HSC 功能及其作为新型药物靶点中的作用的最新认识。