miRNA-130b-5p promotes hepatic stellate cell activation and the development of liver fibrosis by suppressing SIRT4 expression

Liver fibrosis is a progressive disease accompanied by the deposition of extracellular matrix (ECM). Numerous reports have demonstrated that alterations in the expression of microRNAs (miRNAs) are related to liver disease. However, the effect of individual miRNAs on liver fibrosis has not been studied. Hepatic stellate cells (HSCs), being responsible for producing ECM, exert an important influence on liver fibrosis. Then, microarray analysis of non-activated and activated HSCs induced by transforming growth factor beta 1 (TGF-beta 1) showed that miR-130b-5p expression was strongly up-regulated during HSC activation. Moreover, the progression of liver fibrosis had a close connection with the expression of miR-130b-5p in different liver fibrosis mouse models. Then, we identified that there were specific binding sites between miR-130b-5p and the 3 ' UTR of Sirtuin 4 (SIRT4) via a luciferase reporter assay. Knockdown of miR-130b-5p increased SIRT4 expression and ameliorated liver fibrosis in mice transfected with antagomiR-130b-5p oligos. In general, our results suggested that miR-130b-5p promoted HSC activation by targeting SIRT4, which participates in the AMPK/TGF-beta/Smad2/3 signalling pathway. Hence, regulating miR-130b-5p maybe serve as a crucial therapeutic treatment for hepatic fibrosis.

Automated summary

This study identified that the increased expression of miR-130b-5p during hepatic stellate cell activation plays a role in liver fibrosis progression by targeting SIRT4. Regulating miR-130b-5p may serve as a crucial therapeutic strategy for hepatic fibrosis treatment.