Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri.
Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri.
Transl Res. 2019 Dec;214:17-29. doi: 10.1016/j.trsl.2019.07.007. Epub 2019 Aug 13.
Liver fibrosis is a wound-healing process induced by chronic liver injuries, such as nonalcoholic steatohepatitis, hepatitis, alcohol abuse, and metal poisoning. The accumulation of excessive extracellular matrix (ECM) in the liver is a key characteristic of liver fibrosis. Activated hepatic stellate cells (HSCs) are the major producers of ECM and therefore play irreplaceably important roles during the progression of liver fibrosis. Liver fibrogenesis is highly correlated with the activation of HSCs, which is regulated by numerous profibrotic cytokines. Using RNA interference to downregulate these cytokines in activated HSCs is a promising strategy to reverse liver fibrosis. Meanwhile, microRNAs (miRNAs) have also been exploited for the treatment of liver fibrosis. This review focuses on the current siRNA- and miRNA-based liver fibrosis treatment strategies by targeting activated HSCs in the liver.
肝纤维化是由慢性肝损伤引起的一种伤口愈合过程,如非酒精性脂肪性肝炎、肝炎、酒精滥用和金属中毒。肝脏中细胞外基质(ECM)的过度积累是肝纤维化的一个关键特征。活化的肝星状细胞(HSCs)是 ECM 的主要产生者,因此在肝纤维化的进展过程中起着不可替代的重要作用。肝纤维化的发生与 HSCs 的活化高度相关,而 HSCs 的活化受多种促纤维化细胞因子的调节。用 RNA 干扰下调活化的 HSCs 中的这些细胞因子是逆转肝纤维化的一种很有前途的策略。同时,microRNAs(miRNAs)也被用于治疗肝纤维化。本综述重点介绍了目前针对肝内活化的 HSCs 的 siRNA 和 miRNA 为基础的肝纤维化治疗策略。