Retinoid interferon-induced mortality19 (GRIM19) inhibits proliferation and invasion in rheumatoid arthritis fibroblast-like synoviocytes

Abstract

Rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLS) are reportedly involved in RA initiation, progression, and perpetuation. Previously a study showed that retinoid interferon-induced mortality 19 (GRIM19) improved the clinical and histological features of collagen-induced arthritis (CIA),and also inhibited osteoclast formation. However, the role of GRIM19 in RA-FLS remains unclear. In this study, we explored the biological function and underlying mechanism of GRIM19 in cultured RA-FLS. The expression of GRIM19 in synovial tissues and RA-FLS was detected by real-time quantitative RT-PCR(qRT-PCR).The effects of GRIM19 on proliferation, migration, invasion, apoptosis, and inflammatory cytokines levels in RA-FLS were determined using CCK8, wound healing, transwell invasion, and flow cytometry assays, and enzyme-linked immunosorbent assay (ELISA), respectively.GRIM19 and its related protein expression levels were determined by western blot. We found that GRIM19expression was significantly decreased in synovial tissues and FLS from RA patients.GRIM19significantly inhibited proliferation, migration, and invasion; promoted apoptosis; and suppressed inflammatory cytokine secretion by RA-FLS. Moreover, GRIM19 overexpression significantly decreasedthe expression levels of signal transducer and activator of transcription 3(STAT3)and its downstreamproteins,CyclinD1, Bcl-2, and MMP-9. These data indicate that promoting the expression of GRIM19 may yield therapeutic benefits in the treatment of RA.

Keywords: Apoptosis; GRIM19; Proliferation; Rheumatoid arthritis; STAT3.