FNDC4 reduces inflammation, proliferation, invasion and migration of rheumatoid synovial cells by inhibiting CCL2/ERK signaling

Abstract

BackgroundRheumatoid arthritis (RA) is an autoimmune disease characterized by chronic joint inflammation. Fibronectin type III domain-containing protein 4 (FNDC4) is a secretory factor that can regulate inflammatory diseases. However, the role of FNDC4 in RA has not been reported so far. MethodsThe expression of FNDC4 in synovial tissues of RA was analyzed by GEO database (GSE55235 dataset). Then, the expression of FNDC4 in RA fibroblast-like synoviocytes (RA-FLSs) was detected by RT-qPCR and western blot. After constructing FNDC4 overexpression plasmid, cell proliferation and apoptosis were detected. Wound healing and transwell tests were used to detect cell migration and invasion. Then we examined the expression of cytokines related to cell inflammation. Subsequently, the regulatory mechanism of FNDC4 was further discussed. We detected the expression of CCL2 and ERK signaling pathway related proteins downstream of FNDC4. Finally, the mechanism was discussed through the overexpression of FNDC4 and CCL2 and the addition of ERK pathway activator tBHQ. ResultsGEO database showed that FNDC4 expression decreased in synovial tissues of RA. And FNDC4 expression also decreased in RA-FLSs. Overexpression of FNDC4 inhibited the proliferation, invasion and migration of RA-FLSs and promoted its apoptosis. Overexpression of FNDC4 inhibited the release of RA-FLSs inflammatory factors. The regulatory effect of FNDC4 is achieved by inhibiting the CCL2/ERK signaling pathway. ConclusionFNDC4 reduces inflammation, proliferation, invasion and migration of RA-FLSs in RA by inhibiting CCL2/ERK signaling.