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

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.

Bovine Milk-Derived Exosomes as a Drug Delivery Vehicle for miRNA-Based Therapy

“…While a large number of miRNAs have been identified in milk exosomes, several studies indicate that enrichment is only found in a few cases, such as miR-148a-3p ( Supplementary Tables S3 and S4 ). This miRNA is highly expressed in human and bovine milk exosomes ( Supplementary Figure S1 ) and is involved in the regulation of genes associated with different cellular processes [ 49 , 50 , 51 , 52 , 53 ]. Several methods can be used to incorporate molecules to EVs; here, lipofectamine transfection was employed.…”

“…Other studies showed that miR-148a-3p target genes were involved in pathways associated with proliferation [ 51 , 57 ] lipid metabolism [ 53 ] and adipogenesis [ 50 ], among other processes [ 49 , 52 ]. Here, common to these studies, an association with lipid metabolism pathways was identified in the GO analysis.…”

Mesenchymal Stem Cells-derived Exosomal miR-148a-3p Alleviates Atrial Fibrosis and Vulnerability to Atrial Fibrillation Through Targeting ALK5/Smad2 Axis

“…Previous studies suggested that miR-148a-3p targeted ERBB3 to regulate alcoholic liver brosis and the viability of hepatic stellate cells [34]. Moreover, miR-148a-3p targeted Smad2 to regulate the invasion and metastasis of cancer [35].…”

Integrated Analysis of Liver Transcriptome, miRNA, and Proteome of Chinese Indigenous Breed Ningxiang Pig in Three Developmental Stages Uncovers Significant miRNA–mRNA–Protein Networks in Lipid Metabolism

“…It has been reported that exogenous miRNA-143-3p can target the 3′UTR of ANGPTL 8 and regulate the level of high-density lipoprotein cholesterol in hepatocytes ( DiStefano, 2019 ). In addition, miR-21-5p and miR-148a-3p target PDCD4 and ERB 3 , respectively, and are involved in regulating liver cell viability and apoptosis ( Xiong et al, 2020 ; Zhang et al, 2020 ). These identified miRNAs with high expression may play a crucial role in liver development.…”