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Study On The Effect And Mechanism Of S100A4 Inducing VEGF In Fibroblast-like Synoviocytes

Posted on:2021-05-20Degree:MasterType:Thesis
Country:ChinaCandidate:W Y XuFull Text:PDF
GTID:2404330647956946Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objective:To investigate the effect and mechanism of S100A4 Protein in inducing fibroblast-like synoviocytes to express VEGF in the pathogenesis of RA,so as to provide a basis for the early prevention,diagnosis and treatment of RA and the development of specific drugs.Methods:1.Synovium of RA patients who underwent knee arthroscopy or knee arthroplasty in our hospital was selected for isolation and culture of primary synovium fibroblast-like synoviocytes.2.CCK-8 method was used to detect the effect of S100A4 on the proliferation of fibroblast-like synoviocytes.3.The expression of VEGF in RAFLSs was detected by immunofluorescence.4.S100A4 incubation of RAFLSs conditioned medium induced HUVECs to form blood vessels in vitro.5.Western blot was used to detect the effect of S100A4 on RAFLSs m TOR signal pathway.6.Western blot was used to detect the effect of S100A4 on the expression of RAFLSs VEGF protein through m TOR signaling pathway.Results:1.rh S100A4 can promote the proliferation of RAFLSs,and Rap can inhibit the proliferation of RAFLSs by rh S100A4 in a concentration dependent manner.2.rh S100A4 can promote the expression of VEGF protein in a concentration dependent manner,and Rap can inhibit the expression of VEGF protein in rh S100A4.3.rh S100A4 incubation of RAFLSs medium can promote HUVECs to form blood vessels in vitro,with time and concentration dependent effects.Rap can inhibit the above effects.4.rh S100A4 can stimulate RAFLSs,activate the downstream protein S6 of m TOR signaling pathway,and increase its phosphorylation level,which is time and concentration dependent.5.rh S100A4 can activate the downstream protein S6 of m TOR signaling pathway and enhance the expression of VEGF protein,which can be inhibited by Rap.Conclusions:In the course of RA,S100A4 can enhance the VEGF activity of RAFLS,promote the expression of VEGF,lead to the formation of pannus and participate in the development of RA by activating m TOR signal pathway.
Keywords/Search Tags:Rheumatoid arthritis, Rheumatoid arthritis fibroblast like synoviocytes, S100 calcium binding protein A4, mTOR signaling pathway, Vascular endothelial growth factor
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