title: Synoviolin/Hrd1, an E3 ubiquitin ligase, as a novel pathogenic factor for arthropathy.
abstract: Rheumatoid arthritis (RA) is one of the most critical articular diseases with synovial hyperplasia followed by impairment of quality of life. However, the mechanism(s) that regulates synovial cell outgrowth is not fully understood. To clarify its mechanism(s), we carried out immunoscreening by using antirheumatoid synovial cell antibody and identified and cloned "Synoviolin/Hrd1", an E3 ubiquitin ligase. Synoviolin/Hrd1 was highly expressed in the rheumatoid synovium, and mice overexpressing this enzyme developed spontaneous arthropathy. Conversely, synoviolin/hrd1(+/-) mice were resistant to collagen-induced arthritis by enhanced apoptosis of synovial cells. We conclude that Synoviolin/Hrd1 is a novel causative factor for arthropathy by triggering synovial cell outgrowth through its antiapoptotic effects. Our findings provide a new pathogenetic model of RA and suggest that Synoviolin/Hrd1 could be targeted as a therapeutic strategy for RA.
authors.affiliation: Department of Genome Science, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216-8512, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Amano
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamasaki
authors.forename: Naoko
authors.initials: N
authors.lastname: Yagishita
authors.forename: Kaneyuki
authors.initials: K
authors.lastname: Tsuchimochi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shin
authors.forename: Ko-ichi
authors.initials: K
authors.lastname: Kawahara
authors.forename: Satoko
authors.initials: S
authors.lastname: Aratani
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Fujita
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Rie
authors.initials: R
authors.lastname: Ikeda
authors.forename: Ryoji
authors.initials: R
authors.lastname: Fujii
authors.forename: Naoki
authors.initials: N
authors.lastname: Miura
authors.forename: Setsuro
authors.initials: S
authors.lastname: Komiya
authors.forename: Kusuki
authors.initials: K
authors.lastname: Nishioka
authors.forename: Ikuro
authors.initials: I
authors.lastname: Maruyama
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Fukamizu
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nakajima
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001168:Arthritis / Q000139:chemically induced / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D001177:Arthropathy, Neurogenic / Q000235:genetics / Q000473:pathology; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003094:Collagen / Q000009:adverse effects; D004195:Disease Models, Animal; D005260:Female; D015723:Gene Library; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D013583:Synovial Membrane / Q000473:pathology / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D003094:Collagen; D044767:Ubiquitin-Protein Ligases