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Int Immunopharmacol ; 101(Pt B): 108151, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34836796

ABSTRACT

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: Inhibiting miR-181b-5p can promote the expression of PIAS1, thereby inhibiting PRMT1 and ultimately improving AFLD.


Subject(s)
Fatty Liver, Alcoholic/metabolism , Gene Expression Regulation/drug effects , MicroRNAs/metabolism , Protein Inhibitors of Activated STAT/metabolism , Protein-Arginine N-Methyltransferases/metabolism , Animals , Antagomirs/pharmacology , Ethanol/toxicity , Gene Expression Regulation/physiology , Gene Silencing , Male , MicroRNAs/genetics , Oxidative Stress , Protein Inhibitors of Activated STAT/genetics , Protein-Arginine N-Methyltransferases/genetics , Rats , Rats, Wistar , Up-Regulation
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