Role Of Lentivirus-mediated Overexpression Of SOCS3 In Proliferation And Apoptosis Of Fibroblasts-like Synoviocytes In Lewis Rats With Adjuvant-induced Rheumatoid Arthritis

Rheumatoid arthritis(RA)is an autoimmune disease characterized by chronic inflammatory arthropathy.It usually characterized by as pain,swelling and moring stiffness of the joints.Failure to control the disease may eventually lead to serious destruction of the joint structure and deformity.The infiltration of immune cells in the synovium of the joints is its pathological basis.Symptoms may severely affect the work ability and survival of patients.RA is one of the most important diseases threatening human health.The molecular mechanism of RA has always been the focus and difficulty of research.Human SOCS3 is a member of the STAT inhibitory factor(SSI)protein family.It can be used as a negative regulator of STAT cytokine signaling pathway and is overexpressed in synovial cells of patients with RA.It has been proved that high expression of SOCS3 can slow down the progression of RA.Aim: The aim of this study was to elucidate the role of SOCS3 gene expression in the proliferation and apoptosis of fibroblasts-like synoviocytes in rat RA model.Methods:In this study,20 Lewis rats with RA induced by adjuvant were randomly divided into experimental group and control group.28 days later,rats in experimental group were executed.The third generation of fibroblasts-like synoviocytes were collected and transfected into cells by Lentivirus Expression system.According to the different transduction genes,they were divided into SOCS3 group,control group and blank group.MTT colorimetric assay was used to detect cell viability;flow cytometry was used to analyze cell apoptosis;enzyme-linked immunosorbent assay was used to detect the expression of inflammatory factors interleukin-2(IL-2),interferon-gamma(IFN--γ))andtumor necrosis factor(TNF-α);RNA interference was used to silence the expression of endogenous SOCS3 in cells and detect the effect of SOCS3 deletion on cell proliferation.Result: The results showed that compared with the control group and the blank group,the expression of SOCS3 in SOCS3 group increased,and the cells apoptosis decreased.The expression of inflammatory factors IL-2,IFN-γ and TNF-α increased,while silencing the expression of SOCS3 inhibited cell proliferation.This study shows that SOCS3 can significantly promote the proliferation of synovial fibroblasts and inhibit apoptosis in rat rheumatoid arthritis model,thus aggravating the progress of RA.Conclusion: 1.Overexpression of SOCS3 mediated by lentivirus stimulates the proliferation of FLS in rat adjuvant rheumatoid arthritis model;2.Overexpression of SOCS3 mediated by lentivirus inhibits the apoptosis of FLS cells in rat adjuvant rheumatoid arthritis model;3.Overexpression of SOCS3 mediated by lentivirus stimulates the expression of inflammatory factors(IL-2,IFN-γ and TNF-α)in rat adjuvant rheumatoid arthritis model;4.In the rat model of adjuvant rheumatoid arthritis,silencing the expression of SOCS3 mediated by lentivirus inhibited the proliferation of FLS.