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• W4317565616 abstract "Abstract Objective Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease. Over activation of fibroblast-like synoviocytes is responsible for the hyperplasia of synovium and destruction of cartilage and bone and pyroptosis of FLS plays a key role in those pathological processes during RA. This study investigated the detail mechanisms that SMAD2 regulate the pyroptosis of FLS and secrtion of inflammatory factors in rheumatoid arthritis. Methods We collected synovial tissues of RA patients and FLS-RA and cultured FLS for detection of expression of SMAD2. ASC, NLRP3, cleaved-caspase-1 and GSDMD-N were detected by western-blot after over expression of SMAD2. Besides, Flow cytometry, electron microscope, Elisa, HE-staining and Safranin O stainingwere performed to further demonstrated that SMAD2 can affected the pyroptosis of FLS-RA. Results The expression of SMAD2 was down-regulated in synovial tissues of RA patients and FLS-RA. Over expression of SMAD2 can inhibited expression of ASC, NLRP3, cleaved-caspase-1 and GSDMD-N. Flow cytometry and electron microscope further demonstrated that SMAD2 attenuated pyroptosis of FLS-RA. In addition, overexpression of SMAD2 also inhibited inflammatory factors such as IL-1β, IL-18, IL-6 and IL-8 secretion and release of LDH. Besides, overexpression of SMAD2 can reversed the decrease of p-SMAD2 and TGF-TGF-β induced by nigericin. In vivo experiments on CIA rats further demonstrated that overexpression of SMAD2 by local intra-articular injection of LV-SMAD2 can effectively alleviated joint redness, swelling, destruction of cartilage and bones. Conclusion SMAD2 inhibited FLS-RA pyroptosis by down-regulating of NLRP3 inflammasomes (NLRP3, ASC and caspase-1 complex) and eased the secretion of inflammatory factors via TGF-β signaling pathway, thereby improve the symptom of RA. We hope that this study may provide a new research idea for RA and a potential target for treatment of RA." @default.
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• W4317565616 date "2023-01-20" @default.
• W4317565616 modified "2023-09-26" @default.
• W4317565616 title "SMAD2 inhibites pyroptosis of fibroblast-like synoviocytes and secretion of inflammatory factors via TGF-β pathway in rheumatoid arthritis" @default.
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• W4317565616 doi "https://doi.org/10.21203/rs.3.rs-2471290/v1" @default.
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