Kruppel-Like Factor 4 Positively Regulates Autoimmune Arthritis in Mouse Models and Rheumatoid Arthritis in Patients via Modulating Cell Survival and Inflammation Factors of Fibroblast-Like Synoviocyte
Rheumatoid arthritis symptoms (RA) is really a chronic autoimmune ailment that causes mild to severe joint inflammation. During RA pathogenesis, fibroblast-like synoviocytes (FLS) get a tumor-like phenotype and mediate cartilage destruction both directly and not directly by producing proinflammatory cytokines and matrix metalloproteinases (MMPs). Kruppel-like factor (KLF) 4, part of the KLF family, plays significant roles in cell survival, proliferation, and differentiation. Research conducted recently reported elevated expression of KLF4 in synovial tissue from RA patients. However, its precise role in RA in various models, including mouse autoimmune disease models, remains unclear. Within this study, we examined the function of KLF4 during growth and development of autoimmune joint disease in mouse models. To get this done, we used KLF4 knockout rodents made by ribonucleic acidity (RNA)-led endonuclease (RGEN) and performed bovine collagen antibody-caused joint disease (CAIA). We discovered that deletion of KLF4 reduces inflammation caused by CAIA. Additionally, we assessed bovine collagen-caused joint disease (CIA) in charge rodents and KLF4-overexpressing rodents generated with a minicircle vector treatment. Harshness of CIA in rodents overexpressing KLF4 was more than that in rodents injected with control vector. Finally, we verified the inflammatory roles of KLF4 in CIA by treating Kenpaullone which is often used as KLF4 inhibitor. Next, we centered on human/mouse FLS to uncover cellular process involved with RA pathogenesis including proliferation, apoptosis, and inflammation including MMPs. In FLS, KLF4 upregulated expression of mRNA encoding proinflammatory cytokines interleukin (IL)-1ß and IL-6. KLF4 also controlled expression of matrix metallopeptidase 13 within the synovium. We discovered that blockade of KLF4 in FLS elevated apoptosis and covered up proliferation adopted by downregulation of antiapoptotic factor BCL2. Our results indicate that KLF4 plays Kenpaullone a vital role in pathogenesis of inflammatory joint disease in vivo, by controlling apoptosis, MMP expression, and cytokine expression by FLS. Thus, KLF4 may well be a novel transcription factor for generating RA by modulating cellular procedure for FLS.