Department of Pharmacology, Biomedical Research Unit and Laboratory Animal Centre, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), No.162, PH Road, Chennai, Tamil Nadu, 600 077, India.
Eur J Pharmacol. 2020 Oct 15;885:173507. doi: 10.1016/j.ejphar.2020.173507. Epub 2020 Aug 25.
Hepatic stellate cells (HSCs) activation play a significant role in the progression of hepatic fibrosis. During chronic liver diseases, hepatocytes are damaged severely and secrete several pro-inflammatory markers and profibrogenic cytokines via modulation of a variety of signaling pathways that are responsible for the activation of HSCs. The microRNAs (miRNA or miR) have the potential to modulate fibrogenic signaling pathways in HSCs. A variety of miRNAs are identified as profibrogenic and are capable of activating HSCs by modulating fibrosis-associated signaling pathways such as transforming growth factor-β/Smad, Wnt/β-catenin, Hedgehog, Snail and Notch in the injured liver. On the other hand, HSCs also have certain antifibrotic miRNAs and these include miR-16, miR-19b, miR-29, miR-30, miR-101, miR-122, miR-133a, miR-144, miR-146a, miR-150-5p, miR-155, miR-195, miR-200a, miR-214, miR-335, miR-370, miR-454, miR-483, etc. are responsible for maintenance of the quiescent phenotype of normal HSCs, apoptosis induction and phenotypic reversion of activated HSCs, inhibition of HSCs proliferation, suppression of the extracellular matrix-associated gene expressions, etc. Thus, understanding of HSCs specific miRNAs regulation may provide new ideas for the targeted therapy of hepatic fibrosis at molecular level in the near future. Therefore, this review focusses on the modulation of miRNAs profile during the HSCs activation in the fibrotic liver.
肝星状细胞（HSCs）的激活在肝纤维化的进展中起着重要作用。在慢性肝病中，肝细胞受到严重损伤，通过调节多种信号通路分泌多种促炎标志物和促纤维化细胞因子，这些信号通路负责 HSCs 的激活。微小 RNA（miRNA 或 miR）具有调节 HSCs 纤维化信号通路的潜力。多种 miRNA 被鉴定为促纤维化，并能够通过调节纤维化相关信号通路如转化生长因子-β/Smad、Wnt/β-catenin、Hedgehog、Snail 和 Notch 在受损的肝脏中激活 HSCs。另一方面，HSCs 也具有某些抗纤维化的 miRNA，包括 miR-16、miR-19b、miR-29、miR-30、miR-101、miR-122、miR-133a、miR-144、miR-146a、miR-150-5p、miR-155、miR-195、miR-200a、miR-214、miR-335、miR-370、miR-454、miR-483 等，这些 miRNA 负责维持正常 HSCs 的静止表型、诱导激活的 HSCs 凋亡和表型逆转、抑制 HSCs 增殖、抑制细胞外基质相关基因表达等。因此，理解 HSCs 特异性 miRNA 调控可能为肝纤维化的分子靶向治疗提供新的思路。因此，本综述重点介绍了在纤维化肝脏中 HSCs 激活过程中 miRNA 谱的调节。
