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

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.

MicroRNA 200a inhibits liver fibrosis of schistosoma.

MicroRNA 200a (miR-200a) can inhibit the activation and proliferation of hepatic stellate cells (HSCs) through the transforming growth factor-ß (TGF-ß) signaling pathway, and improve fibrotic lesions. However, to date, there is no study exploring the role of miR-200a in schistosomiasis liver fibrosis (SLF). In this study, 64 healthy female Balb/c mice were selected and randomly divided into four groups: normal control group (non-infected schistosomiasis group), schistosomiasis model group, Lenti-NC group (lentivirus-negative control group), and Lenti-miR-200a group (lentivirus experimental group). Fluorescence quantitative PCR detection was used to measure the expression level of RNA. HE and Masson staining were used to observe the pathological changes of mouse liver tissue. Furthermore, ELISA was used to detect the serum concentrations of inflammation factors. We found that the expression level of miR-200a in liver tissues gradually decreased with the development of SLF. However, fibrosis factors (α-SMA and TGF-ß2) and inflammatory cytokines (IL-4 and IFN-γ) in liver tissues and serum increased and the expression level of Colla I reached its peak in the 6th week of infection. Besides, compared with the schistosomiasis group and Lenti-NC group, the Lenti-NC group had lower levels of α-SMA, TGF-ß2 and Colla I (P > 0.05). Furthermore, inflammatory cells and blue collagen fibers appeared and they increased with the development of infection in the schistosomiasis group and Lenti-NC group, but these changes reduced significantly in Lenti-miR-200a group. Our study demonstrated that upregulation of miR-200a might contribute to inhibiting schistosomiasis liver fibrosis.