title: uPAR promotes tumor-like biologic behaviors of fibroblast-like synoviocytes through PI3K/Akt signaling pathway in patients with rheumatoid arthritis.
abstract: 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 with β1-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 the β1-integrin/PI3K/Akt signaling pathway. These results imply that targeting uPAR and its downstream signal pathway may provide therapeutic effects in RA.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.|Department of Clinical Immunology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.|Department of Clinical Immunology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.
authors.forename: Yun Feng
authors.initials: YF
authors.lastname: Pan
authors.affiliation: Department of Clinical Immunology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.
authors.forename: You-Qiu
authors.initials: YQ
authors.lastname: Xue
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.
authors.forename: Lin-Kai
authors.initials: LK
authors.lastname: Fang
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Guo
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, The Second People's Hospital of Guangdong Province, Guangzhou 510310, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, The Second People's Hospital of Guangdong Province, Guangzhou 510310, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Liu
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.
authors.forename: Bi-Yao
authors.initials: BY
authors.lastname: Mo
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.
authors.forename: Meng-Ru
authors.initials: MR
authors.lastname: Yang
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Division of Neurology, Department of Internal Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.
authors.forename: Yun-Ting
authors.initials: YT
authors.lastname: Wu
authors.affiliation: Division of Rheumatology, Department of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Olsen
authors.affiliation: Department of Clinical Immunology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.|Division of Rheumatology, Department of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
authors.forename: Song Guo
authors.initials: SG
authors.lastname: Zheng
mesh_terms: D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D004705:Endocytosis; D042783:Endothelial Cells / Q000378:metabolism; D005347:Fibroblasts / Q000473:pathology*; D055785:Gene Knockdown Techniques; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D016086:Lentivirus / Q000378:metabolism; D009369:Neoplasms / Q000473:pathology*; D010003:Osteoarthritis / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000070918:Synoviocytes / Q000473:pathology*
chemical_list: D019012:Integrin beta1; D012333:RNA, Messenger; D055293:Receptors, Urokinase Plasminogen Activator; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt