Rheumatoid arthritis as a hyper-endoplasmic reticulum-associated degradation disease |
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Authors: | Satoshi?Yamasaki Naoko?Yagishita Kaneyuki?Tsuchimochi Kusuki?Nishioka Email author" target="_blank">Toshihiro?NakajimaEmail author |
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Institution: | (1) Department of Genome Science, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan;(2) Rheumatology, Immunology and Genetics Program, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan; |
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Abstract: | We introduce Synoviolin as a novel pathogenic factor in rheumatoid arthritis (RA). Experimental studies indicate that this
endoplasmic reticulum (ER)-resident E3 ubiquitin ligase has important functions in the ER-associated degradation (ERAD) system,
an essential system for ER homeostasis. Overexpression of Synoviolin in mice causes arthropathy with synovial hyperplasia,
whereas heterozygous knockdown results in increased apoptosis of synovial cells and resistance to collagen-induced arthritis
in mice. On the basis of these experimental data, we propose that excess elimination of unfolded proteins (that is, 'hyper-ERAD')
by overexpression of Synoviolin triggers synovial cell overgrowth and hence a worsening of RA. Further analysis of the hyper-ERAD
system may permit the complex pathomechanisms of RA to be uncovered. |
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