Resistance to endoplasmic reticulum stress is an acquired cellular characteristic of rheumatoid synovial cells.
Synoviolin is an endoplasmic reticulum (ER)-resident E3 ubiquitin ligase which plays a critical role in ER-associated degradation (ERAD). We found that Synoviolin is a novel causative factor for rheumatoid arthritis (RA), which is especially up-regulated in proliferating synovial cells in the disease. We attempted to examine the role of Synoviolin in ER stress-induced apoptosis and proliferation of synovial cells. RA synovial cells (RSCs) were refractory to ER stress-induced apoptosis compared with HEK293 or HeLa cells. RSCs were also more resistant to the apoptosis than synovial cells from osteoarthritis patients, significantly. Down-regulation of Synoviolin by siRNA increased the susceptibility to ER stress-induced apoptosis in RSCs. Knock-down of Synoviolin by siRNA did not only induce apoptosis of RSCs but also inhibited their proliferation in vitro. These data suggest that RSCs are extraordinarily refractory to ER stress-induced apoptosis, and we termed this special property 'hyper-ERAD'. Since Synoviolin is overexpressed in RSCs, and is known to play a critical role in the ERAD system as E3 ubiquitin ligase, hyper-ERAD is likely to present in these cells. Subsequently, the hyper-ERAD may cause synovial hyperplasia through its anti-apoptotic effect in RA. Further analyses are necessary to address this point, however, resistance to ER stress-induced apoptosis, or hyper-ERAD is a noteworthy new cellular characteristic of RSCs.
Yamasaki
Satoshi
S
Department of Genome Science, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216-8512, Japan.
Yagishita
Naoko
N
Tsuchimochi
Kaneyuki
K
Kato
Yukihiro
Y
Sasaki
Takeshi
T
Amano
Tetsuya
T
Beppu
Moroe
M
Aoki
Haruhito
H
Nakamura
Hiroshi
H
Nishioka
Kusuki
K
Nakajima
Toshihiro
T
D017209:Apoptosis / Q000502:physiology; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
D034741:RNA, Small Interfering; C482345:SYVN1 protein, human; D044767:Ubiquitin-Protein Ligases