Foxc1 promotes the proliferation of fibroblast-like synoviocytes in rheumatoid arthritis via PI3K/AKT signalling pathway

Abstract Forkhead box c1 (Foxc1) is a vital member of the Fox family of transcription factors which play important roles in numerous biological processes including metabolism, differentiation, proliferation, apoptosis, migration, invasion and longevity. However, up to date, the role of Foxc1 in the development of Rheumatoid Arthritis (RA) has not been fully elucidated. In the present study, the markedly higher expression of Foxc1 was observed in fibroblast-like synoviocytes (FLSs) of RA compared to control. Besides, we found that Foxc1 had a co-localization with THY1 (a marker for fibroblast-like synoviocytes). Moreover, during the process of TNF-α-induced inflammatory response model, Foxc1 was progressively accumulated in FLSs which was in parallel with MMP-1, MMP-13. Consistently, cell inflammatory response was distinctly hindered by small interfering RNA. Even more importantly, we discovered that Foxc1 promoted cell proliferation by upregulation PI3K/AKT signaling, which was inflammation-dependent. In summary, these data implied that Foxc1 might regulates fibroblast-like synoviocytes proliferation by reducing PI3K/AKT signaling pathway and all above findings provide novel therapeutic effects in the treatment for RA patients.