miR‑148a‑3p regulates alcoholic liver fibrosis through targeting ERBB3

Xiong,Jie; Ni,Jianbo; Chen,Congying; Wang,Kezhou

doi:10.3892/ijmm.2020.4655

miR‑148a‑3p regulates alcoholic liver fibrosis through targeting ERBB3

Authors:
- Jie Xiong
- Jianbo Ni
- Congying Chen
- Kezhou Wang
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Affiliations: Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, P.R. China, Department of Gastroenterology and Hepatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China, Department of Pathology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China
Published online on: June 23, 2020 https://doi.org/10.3892/ijmm.2020.4655
Pages: 1003-1012
Copyright: © Xiong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Alcoholic liver disease greatly affects human health. Previous studies have identified that microRNAs (miRNAs) are associated with the pathogenesis of alcoholic liver fibrosis (ALF). Therefore, the present study explored the regulatory mechanism of miR‑148a‑3p in ALF. An ALF model was established in rats by alcohol gavage, followed by treatment with miR‑148a‑3p. Reverse transcription‑quantitative (RT‑q) PCR was performed to detect miR‑148a‑3p expression in the rat liver tissues. The levels of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were determined by enzyme‑labeled colorimetry. Liver damage was evaluated by liver indices and histology. The direct target gene of miR‑148a‑3p was predicted by a dual luciferase reporter assay. The effects of miR‑148a‑3p and miR‑148a‑3p in combination with receptor tyrosine‑protein kinase erbB‑3 (ERBB3) on HSC‑T6 cell viability and apoptosis were detected by MTT and flow cytometry assays, respectively. Western blotting and RT‑qPCR assays were performed to detect the expression levels of proteins and mRNA associated with fibrosis and apoptosis. The data showed that miR‑148a‑3p mimics inhibited the expression levels of AST, ALT, ALP, LDH, α‑SMA and type I collagen in the model, decreased the liver indices, and improved the liver damage caused by alcohol. ERBB3, which was predicted as the direct target gene of miR‑148a‑3p, reversed the effects of ERBB3 on promoting cell viability and inhibiting apoptosis. Concomitantly, miR‑148a‑3p reversed the increased expression of Bcl‑2 and inhibited the expression levels of Bax and c‑cleaved‑3 caused by ERBB3. These data suggested that miR‑148a‑3p regulated ALF and the viability and apoptosis of hepatic stellate cells through targeting ERBB3.

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