Open AccessmiRNA‐130b‐5p promotes hepatic stellate cell activation and the development of liver fibrosis by suppressing SIRT4 expression
Author(s) -
Wang Hao,
Wang Zeng,
Wang Yirui,
Li Xiangcheng,
Yang Wenjie,
Wei Song,
Shi Chengyu,
Qiu Jiannan,
Ni Ming,
Rao Jianhua,
Cheng Feng
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16766
Subject(s) - hepatic stellate cell , fibrosis , microrna , gene knockdown , hepatic fibrosis , cancer research , sirtuin , transforming growth factor , extracellular matrix , biology , microbiology and biotechnology , chemistry , pathology , medicine , endocrinology , apoptosis , biochemistry , gene , acetylation
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 β1 (TGF‐β1) 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‐β/Smad2/3 signalling pathway. Hence, regulating miR‐130b‐5p maybe serve as a crucial therapeutic treatment for hepatic fibrosis.