title: The proto-oncogene survivin splice variant 2B is induced by PDGF and leads to cell proliferation in rheumatoid arthritis fibroblast-like synoviocytes.
abstract: Survivin is an independent prognostic factor for joint destruction in rheumatoid arthritis (RA). However, the expression and function of survivin in RA synoviocytes remain unclear. We certified the expression of survivin in RA synovial tissues and performed the experiment using RA fibroblast-like synoviocytes (RA-FLS) treated with siRNA. As a result, the expression levels of wild type (WT) survivin and the 2B splice variants in RA synovial tissues were higher than those in osteoarthritis tissue samples, and, these variants were highly expressed in RA-FLS. The expression levels of survivin-WT and -2B in the RA-FLS were upregulated by PDGF. Treatment with siRNA against survivin-2B led to decreased viability of PDGF-treated RA-FLS due to cell cycle suppression and apoptosis promotion, while the siRNA against all survivin isoforms did not affect the viability. Moreover, an overexpression of survivin-2B in RA-FLS led to cell proliferation through cell cycle activation and by conferring resistance to apoptosis. In conclusion, survivin-2B has an important role in RA-FLS proliferation. These data suggest that survivin-2B might contribute to rheumatoid synovial hyperplasia, and have the potential as a novel therapeutic target for RA.
authors.affiliation: 1] Department of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan [2] Department of Internal Medicine, Center for Rheumatic Diseases, Dohgo Spa Hospital, Matsuyama, Japan [3] Department of Pathology, Ehime University Proteo-Science Centre and Graduate School of Medicine, Toon, Japan [4] Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Mokuda
authors.affiliation: Department of Pathology, Ehime University Proteo-Science Centre and Graduate School of Medicine, Toon, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Department of Pathology, Ehime University Proteo-Science Centre and Graduate School of Medicine, Toon, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamasaki
authors.affiliation: Department of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Department of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Yun
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Weng-Sheng
authors.initials: WS
authors.lastname: Kong
authors.affiliation: Department of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Masamoto
authors.initials: M
authors.lastname: Kanno
authors.affiliation: Department of Internal Medicine, Center for Rheumatic Diseases, Dohgo Spa Hospital, Matsuyama, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takasugi
authors.affiliation: Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Sugiyama
authors.affiliation: Department of Pathology, Ehime University Proteo-Science Centre and Graduate School of Medicine, Toon, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Masumoto
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology; D000077214:Becaplermin; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D012326:RNA Splicing; D034741:RNA, Small Interfering / Q000378:metabolism; D000077022:Survivin; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D053583:Interleukin-1beta; D020738:Leptin; C000715470:MAS1 protein, human; D020033:Protein Isoforms; D000090063:Proto-Oncogene Mas; D020574:Proto-Oncogene Proteins c-sis; D034741:RNA, Small Interfering; D000077022:Survivin; D014409:Tumor Necrosis Factor-alpha; D000077214:Becaplermin