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miR-182-5p Attenuates High-Fat -Diet-Induced Nonalcoholic Steatohepatitis in Mice

Qionghe Liang, Huan Chen, Xiaoqun Xu, Weiwei Jiang

Abstract

Introduction and aim. Patients with NASH have increased risk for sepsis or cardiovascular disease after Liver transplantation. An important role of Toll-like receptor (TLR) 4 in the pathogenesis of nonalcoholic steatohepatitis (NASH) was demonstrated. Here, we study the role of miR-182-5p in TLR4 expression and high-fat-diet (HFD)-induced NASH in vitro and in vivo. Material and methods. Following transfection with a miR-182-5p mimic, the effect of miR-182-5p on TLR4 in RAW264.7 and HepG2 cells was investigated. Following administration of the miR-182-5p mimic into the livers of HFD-induced NASH mice, we determined the in vivo expression of TLR4, TNFα, and IL-6 and assessed the histologic features of the livers. Results. Following lipopolysaccharide (LPS) treatment of RAW264.7 cells, real-time RT-PCR and western blot results indicated decreases levels of TLR4 mRNA and protein in the miR-182-5p group as compared with levels observed in controls, with similar trends were observed in TNFα and IL-6 protein levels. Following oleic acid (OA) treatment of HepG2 cells, TLR4, TNFα, and IL-6 levels were significantly decreased in the miR-182-5p group as compared with levels observed in controls. Following miR-182-5p administration, TLR4 mRNA and protein levels decreased along with those of TNFα and IL-6 proteins, and the liver weight/body weight ratio of treated mice was less than that observed in controls. Furthermore, hematoxylin and eosin staining showed that the miR-182-5p-treated group exhibited low adipose cell cross-sectional areas, and Oil Red O staining showed decreases in the size of lipid droplets in the miR-182-5p-treated group. Conclusions. miR-182-5p ameliorated HFD-induced NASH by suppressing TLR4.

Key words. miR-182-5p, Non-alcoholic fatty liver disease, Non-alcoholic steatohepatitis, Toll-like receptor 4

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The Official Journal of the Mexican Association of Hepatology, the Latin-American Association for the Study of the Liver and the Canadian Association for the Study of the Liver

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