Ameliorative Effect of miR-31 on Liver Injury in Type 2 Diabetic Mice
10.13865/j.cnki.cjbmb.2022.07.1139
- Author:
Yuan FU
1
;
Yu-Fei WANG
1
;
Jin-Feng HE
1
;
Xuan-Ping ZHANG
1
;
Ruo-Chen DU
2
;
Yi-Tong YUAN
2
;
Yu-Juan ZHANG
2
;
Chun-Fang WANG
2
Author Information
1. Department of Pharmacology, School of Basic Medicine, Shanxi Medical University
2. Laboratory Animal Center, Shanxi Medical University
- Publication Type:Journal Article
- Keywords:
endoplasmic reticulum stress (ER stress);
liver injury;
microRNA (miRNA);
miR-31;
type 2 diabetes mellitus (T2DM)
- From:
Chinese Journal of Biochemistry and Molecular Biology
2022;38(9):1226-1233
- CountryChina
- Language:Chinese
-
Abstract:
Type 2 diabetes mellitus (T2DM) is a metabolic disease with an increasing incidence worldwide, which leads to damage to various tissues and organs including the liver. MiR-31 is conserved across species and closely associated with metabolic diseases, but its role in type 2 diabetic liver injury has not been elucidated. This study aimed to investigate the effect of miR-31 on liver injury in type 2 diabetes and its underlying mechanism. Four to six weeks old male FVB mice and miR-31-positive transgenic mice were randomly divided into FVB mice control group (C), FVB mice induced diabetes group (DM) and miR-31-overexpression transgenic mice induced diabetes group (31DM). After 1 week of adaptive feeding, the T2DM mouse model was induced by high-fat feeding combined with intraperitoneal injection of streptozotocin (STZ) for 6 weeks. The general condition of mice and related metabolic indicators showed that the increased food and water intake, weight loss and glucose and lipid metabolism disorders could be reversed by miR-31 in T2DM mice. HE staining and liver histological activity index (HAI) scoring results showed that miR-31 improved the inflammatory status in the liver tissue of T2DM mice and decreased the HAI score. RT-qPCR results showed that the high expression of miR-31 was accompanied by a decrease in the expression of activating transcription factor 6 (ATF6) mRNA in the liver of T2DM mice. Furthermore, Western blotting results showed that miR-31 inhibited the expression of endoplasmic reticulum stress-related proteins such as ATF6, glucoregulatory protein 78 (GRP78) and C/EBP homologous protein (CHOP) in the liver of T2DM mice. In conclusion, miR-31 may ameliorate liver injury in T2DM mice by regulating glucose and lipid metabolism disorders and insulin resistance, and inhibiting endoplasmic reticulum stress factors such as ATF6, GRP78, and CHOP.