MiR-451 inhibits synovial fibroblasts proliferation and inflammatory cytokines secretion in rheumatoid arthritis through mediating p38MAPK signaling pathway.

Abstract

Rheumatoid arthritis is an autoimmune disease characterized as joint synovial inflammation. MicroRNA is a group of small noncoding RNA molecules discovered in recent years that can posttranscriptional regulate mRNA expression and involved in a variety processes of immune cell activation and differentiation. There is still lack of study about the role of miR-451 in rheumatoid arthritis. Synovial fibroblasts isolated from rheumatoid arthritis patients were cultured in vitro. Chemical synthesized miR-451 was lipo-transfected, real-time RT-PCR was applied to detect miR-451 expression level, and MTT method was used to detect the effect of miR-451 on synovial fibroblasts proliferation. Enzyme-linked immunosorbent assay was used to detect tumor necrosis factor TNF-α, IL-1β, and IL-6 level in the supernatant. Western blot was applied to test target protein p38 MAPK expression level. Our study found that synovial fibroblasts expressed higher miR-451 mRNA level in miR-451 treatment group. MiR-451 treatment significantly decreased cell proliferation ability (P < 0.05). Compared with the control, p38 MAPK protein expression reduced obviously in the miR-451 treatment group (P < 0.05). MiR-451 transfected synovial fibroblasts secreted lower levels of TNF-α (198 ± 12 pg/ml vs 124 ± 13 pg/ml, P < 0.01), IL-1β (352 ± 43 pg/ml vs 165 ± 87 pg/ml, P < 0.01), and IL-6 (487 ± 84 pg/ml vs 257 ± 92 pg/ml, P < 0.01). The results proved that miR-451 can down-regulate p38 MAPK protein expression, and reduce synovial fibroblasts proliferation and cytokine expression level.