Inhibition of Kruppel-like factor 7 attenuates cell proliferation and inflammation of fibroblast-like synoviocytes in rheumatoid arthritis through nuclear factor κB and mitogen-activated protein kinase signaling pathway

Rheumatoid arthritis (RA) is an autoimmune disease, which can lead to joint inflammation and progressive joint destruction. Kruppel-like factor 7 (KLF7) is the member of KLF family and plays an important role in multiple biological progresses. However, its precise roles in RA have not been described. Present study aimed to investigate the role of KLF7 in RA-fibroblast-like synoviocytes (FLSs). Data showed that KLF7 expression was obviously upregulated in synovial tissues of rats with adjuvant-induced arthritis. Functional studies demonstrated that the loss of KLF7 may suppress cell proliferation and the expression of pro-inflammatory factors (IL-6, IL-1 beta, IL-17A) and matrix metalloproteinase (MMP-1, MMP-3, MMP-13) in FLSs through the inhibition of phosphorylation of nuclear factor kappa B (NF-kappa B) p65 and JNK. We further showed that miR-9a-5p specifically interacts with KLF7 to negatively regulate the expression of KLF7 in RA-FLSs. Taken together, our results demonstrated that KLF7 which targeted by miR-9a-5p might participate in the pathogenesis of RA by promoting cell proliferation, pro-inflammatory cytokine release and MMP expression through the activation of NF-kappa B and JNK pathways in RA-FLSs. Hence, KLF7 could be a novel target for RA therapy.

Automated summary

RA is an autoimmune disease that can cause joint inflammation and destruction. KLF7 expression was found to be upregulated in synovial tissues of rats with arthritis, and its loss suppressed cell proliferation, pro-inflammatory factors, and MMP expression in FLSs through inhibition of NF-kappa B and JNK pathways. miR-9a-5p negatively regulated KLF7 expression, suggesting a potential role for KLF7 as a therapeutic target for RA.