MiR-30a-3p ameliorates oxidative stress in rheumatoid arthritis synovial fibroblasts via activation of Nrf2-ARE signaling pathway

Abstract

The downregulation of miR-30a-3p has been reported in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS); however, it is poorly understood its possible involvement and the underlying mechanism. The effects of miR-30a-3p overexpression on the proliferation and apoptosis as well as oxidative stress injury were evaluated in rats RA-FLS. The targeting relationship between miR-30a-3p and Kelch-like erythroid cell-derived protein with CNC homology (ECH)-associated protein 1 (Keap1) or cullin3 (cul3) was assessed by luciferase reporter assays. The reduced expression of miR-30a-3p was observed in hydrogen peroxide (H2O2)-treated rat RA-FLS. Functional analysis indicated that the restoration of miR-30a-3p expression reversed H2O2-induced FLS proliferation and oxidative stress and induced apoptosis. Mechanistic analyses further revealed that Keap1 and cul3 were both downstream targets of miR-30a-3p. Further investigation indicated that miR-30a-3p agomir exerted anti-arthritic effects on adjuvant-induced arthritis (AA) in rats. Targeting Keap1 or cul3 by miR-30a-3p activated nuclear factor erythroid 2-related factor 2 (Nrf2) signaling to protect FLS against oxidative stress. The miR-30a-3p/Nrf2-Keap1-cul3 pathway axis might be a potential therapy for RA.