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Silencing miR-181b-5p upregulates PIAS1 to repress oxidative stress and inflammatory response in rats with alcoholic fatty liver disease through inhibiting PRMT1

•MiR-181b-5p and PRMT1 are upregulated while PIAS1 is downregulated in AFLD.•Inhibited miR-181b-5p/PRMT1 or overexpressed PIAS1 improves AFLD.•MiR-181b-5p targets PIAS1.•PIAS1 negatively regulates PRMT1.•This study may provide novel targets for AFLD treatment. This study aimed to probe the function...

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Published in:International immunopharmacology 2021-12, Vol.101, p.108151-108151, Article 108151
Main Authors: Wang, Wei, Zhong, Guan-Zhen, Long, Kai-Bing, Liu, Yang, Liu, Ya-Qian, Xu, Ai-Lei
Format: Article
Language:English
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Summary:•MiR-181b-5p and PRMT1 are upregulated while PIAS1 is downregulated in AFLD.•Inhibited miR-181b-5p/PRMT1 or overexpressed PIAS1 improves AFLD.•MiR-181b-5p targets PIAS1.•PIAS1 negatively regulates PRMT1.•This study may provide novel targets for AFLD treatment. This study aimed to probe the function of microRNA-181b-5p (miR-181b-5p)/protein inhibitor of activated STAT1 (PIAS1)/protein arginine methyltransferase 1 (PRMT1) axis in the progression of alcoholic fatty liver disease (AFLD). A rat model of AFLD was established and treated with altered miR-181b-5p, PIAS1 or PRMT1 expression constructs to identify their effects on liver function, serum inflammation, liver tissue oxidative stress, hepatocyte apoptosis and pathological changes of liver tissue in rats using a series of assays. miR-181b-5p, PIAS1 and PRMT1 levels were detected, and the targeting relationship between miR-181b-5p and PIAS1 was confirmed. MiR-181b-5p and PRMT1 were elevated while PIAS1 was reduced in AFLD rat liver tissues, miR-181b-5p inhibition, PIAS1 overexpression or PRMT1 inhibition improved liver function, attenuated inflammation, oxidative stress, pathological changes and hepatocyte apoptosis in AFLD rat liver tissues. The impacts of miR-181b-5p inhibition on AFLD rats were reversed by PIAS1 silencing. PIAS1 was confirmed as a target gene of miR-181b-5p, and miR-181b-5p regulated PRMT1 expression through binding to PIAS1. Inhibiting miR-181b-5p can promote the expression of PIAS1, thereby inhibiting PRMT1 and ultimately improving AFLD.
ISSN:1567-5769
1878-1705
DOI:10.1016/j.intimp.2021.108151