Urokinase-type plasminogen activator receptor(uPAR),is a multifunctional receptor on cell surface,widely present in endothelial cells,fibroblasts,and a variety of malignant cells.Current studies have suggested that uP...Urokinase-type plasminogen activator receptor(uPAR),is a multifunctional receptor on cell surface,widely present in endothelial cells,fibroblasts,and a variety of malignant cells.Current studies have suggested that uPAR overexpressed on synovial tissues or in synovial fluid or plasma in patients with rheumatoid arthritis(RA).However,there are limited researches regarding the role of uPAR on fibroblast-like synoviocytes of rheumatoid arthritis(RA-FLSs)and its underlying mechanisms.Here,our studies show that the expression of uPAR protein was significantly higher in fibroblast-like synoviocytes(FLSs)from RA than those from osteoarthritis or traumatic injury patients.uPAR gene silencing significantly inhibited RA-FLSs cell proliferation,restrained cell transformation from the G0/G1 phase to S phase,aggravated cell apoptosis,interfered with RA-FLSs cell migration and invasion,and reduced activation of the PI3K/Akt signaling pathway,which may be associated withβ1-integrin.Cell supernatants from uPAR gene-silenced RA-FLSs markedly inhibited the migration and tubule formation ability of the HUVECs(a human endothelial cell line).Therefore,we demonstrate that uPAR changes the biological characteristics of RA-FLSs,and affects neoangiogenesis of synovial tissues in patients with RA.All of these may be associated with theβ1-integrin/PI3K/Akt signaling pathway.These results imply that targeting uPAR and its downstream signal pathway may provide therapeutic effects in RA.展开更多
基金This work was supported in part by the grants from Science and Technology Planning Project of Guangdong Province,China(2012B031800363)Science and Technology Program of Guangzhou,China(Special Project on the Integration of Industry,Education and Research)+2 种基金Developing Program of the Major Research Plan of the National Natural Science Foundation of Guangdong,China(2014A030308005)National Natural Science Foundation of China(81671611)and Major National developing program of the national level in Higher Education of Guangdong,China(Natural Science).
文摘Urokinase-type plasminogen activator receptor(uPAR),is a multifunctional receptor on cell surface,widely present in endothelial cells,fibroblasts,and a variety of malignant cells.Current studies have suggested that uPAR overexpressed on synovial tissues or in synovial fluid or plasma in patients with rheumatoid arthritis(RA).However,there are limited researches regarding the role of uPAR on fibroblast-like synoviocytes of rheumatoid arthritis(RA-FLSs)and its underlying mechanisms.Here,our studies show that the expression of uPAR protein was significantly higher in fibroblast-like synoviocytes(FLSs)from RA than those from osteoarthritis or traumatic injury patients.uPAR gene silencing significantly inhibited RA-FLSs cell proliferation,restrained cell transformation from the G0/G1 phase to S phase,aggravated cell apoptosis,interfered with RA-FLSs cell migration and invasion,and reduced activation of the PI3K/Akt signaling pathway,which may be associated withβ1-integrin.Cell supernatants from uPAR gene-silenced RA-FLSs markedly inhibited the migration and tubule formation ability of the HUVECs(a human endothelial cell line).Therefore,we demonstrate that uPAR changes the biological characteristics of RA-FLSs,and affects neoangiogenesis of synovial tissues in patients with RA.All of these may be associated with theβ1-integrin/PI3K/Akt signaling pathway.These results imply that targeting uPAR and its downstream signal pathway may provide therapeutic effects in RA.
