MiR-19 suppresses fibroblast-like synoviocytes cytokine release by targeting toll like receptor 2 in rheumatoid arthritis

MiR-19 通过靶向 Toll 样受体 2 抑制类风湿关节炎中的成纤维细胞样滑膜细胞细胞因子释放

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作者:Zongyu Li, Jinfang Cai, Xuecheng Cao

Abstract

Fibroblast-like synoviocytes (FLS) play an important role in the pathogenesis of rheumatoid arthritis (RA) through participating in joint tissue inflammation and joint damage. MicroRNAs are a kind of small non-coding RNAs that can regulate gene expression in the transcription level to affect cell behaviors. This study intended to investigate the expression of miR-19 in FLS from RA patients and related mechanism. A total of 126 RA patients were selected in this study. MiR-19 expression in FLS was detected by qRT-PCR. Toll like receptor 2 (TLR2) protein expression was tested by Western blot. MiR-19 target genes were confirmed by bioinformatics analysis and luciferase reporter assay. The impact of miR-19 on the expression of TLR2, interleukin 6 (IL-6), and matrix metalloproteinase 3 (MMP-3) in FLS were analyzed by cell transfection and Western blot. MiR-19 expression in FLS from RA patients was significantly downregulated compared with control (P < 0.05), while TLR2 level was increased (P < 0.05). Bioinformatics analysis and luciferase reporter assay confirmed that TLR2 was the target gene of miR-19. Transfection of miR-19 mimic or miR-19 inhibitor obviously suppressed or increased TLR2 expression, and reduced or promoted release of cytokines IL-6 and MMP-3 in FLS, respectively. In conclusion, MiR-19 expression was downregulated in FLS from RA patients, leading to increased TLR2 expression and enhanced cytokines release.

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