MicroRNA-30b regulates insulin sensitivity by targeting SERCA2b in non-alcoholic fatty liver disease.
Autor: | Dai LL; State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming, China., Li SD; Department of Biochemistry and Molecular Biology, College of Basic Medicine, Kunming Medical University, Kunming, China., Ma YC; State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming, China., Tang JR; The First Affiliated Hospital, Yunnan Institute of Digestive Disease, Kunming Medical University, Kunming, China., Lv JY; The First Affiliated Hospital, Yunnan Institute of Digestive Disease, Kunming Medical University, Kunming, China., Zhang YQ; The First Affiliated Hospital, Yunnan Institute of Digestive Disease, Kunming Medical University, Kunming, China., Miao YL; The First Affiliated Hospital, Yunnan Institute of Digestive Disease, Kunming Medical University, Kunming, China., Ma YQ; The First Affiliated Hospital, Yunnan Institute of Digestive Disease, Kunming Medical University, Kunming, China., Li CM; The First Affiliated Hospital, Yunnan Institute of Digestive Disease, Kunming Medical University, Kunming, China., Chu YY; The First Affiliated Hospital, Yunnan Institute of Digestive Disease, Kunming Medical University, Kunming, China., Wang KH; The First Affiliated Hospital, Yunnan Institute of Digestive Disease, Kunming Medical University, Kunming, China., Ma LQ; The First Affiliated Hospital, Yunnan Institute of Digestive Disease, Kunming Medical University, Kunming, China., Zou CG; State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming, China. |
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Jazyk: | angličtina |
Zdroj: | Liver international : official journal of the International Association for the Study of the Liver [Liver Int] 2019 Aug; Vol. 39 (8), pp. 1504-1513. Date of Electronic Publication: 2019 Mar 18. |
DOI: | 10.1111/liv.14067 |
Abstrakt: | Background & Aims: Insulin resistance is strongly associated with non-alcoholic fatty liver disease, a chronic, obesity-related liver disease. Increased endoplasmic reticulum (ER) stress plays an important role in the development of insulin resistance. In this study, we investigated the roles of miRNAs in regulating ER stress in the liver of rats with obesity. Methods: We used miRNA microarray to determine the miRNA expression profiles in the liver of rats fed with a high fat diet (HFD). We used prediction algorithms and luciferase reporter assay to identify the target gene of miRNAs. To overexpress the miRNA miR-30b or inhibit miR-30b rats were injected with lentivirus particles containing PGLV3-miR-30b or PGLV3-miR-30b antimiR through tail vein. Hepatic steatosis was measured using transient elastography in human subjects. Results: Our data showed that miR-30b was markedly up-regulated in the liver of HFD-treated rats. Bioinformatic and in vitro and in vivo studies led us to identify sarco(endo)plasmic reticulum Ca 2+ -ATPase 2b (SERCA2b), as a novel target of miR-30b. Overexpression of miR-30b induced ER stress and insulin resistance in rats fed with normal diet, whereas inhibition of miR-30b by miR-30b antimiR suppressed ER stress and insulin resistance in HFD-treated rats. Finally, our data demonstrated that there was a positive correlation between serum miR-30b levels and hepatic steatosis or homoeostasis model assessment of insulin resistance (HOMA-IR) in human subjects. Conclusions: Our findings suggest that miR-30b represents not only a potential target for the treatment of insulin resistance, but also a non-invasive disease biomarker of NAFLD. (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.) |
Databáze: | MEDLINE |
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