Rheumatoid arthritis as a hyper-endoplasmic reticulum-associated degradation disease 英文参考文献.docVIP

Available online /content/7/5/181 Commentary Rheumatoid arthritis as a hyper-endoplasmic reticulum- associated degradation disease Satoshi Yamasaki1, Naoko Yagishita1, Kaneyuki Tsuchimochi1, Kusuki Nishioka2 and Toshihiro Nakajima1 1Department of Genome Science, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan 2Rheumatology, Immunology and Genetics Program, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan Corresponding author: Toshihiro Nakajima, nakashit@marianna-u.ac.jp Published: 17 August 2005 Arthritis Research Therapy 2005, 7:181-186 (DOI 10.1186/ar1808) This article is online at /content/7/5/181 ? 2005 BioMed Central Ltd Abstract degradation (ERAD) system [12-17]. ERAD is an important processing system for ER homeostasis, and its disruption is known to result in cellular apoptosis [18]. Surprisingly, both the amount and enzymatic activity of Synoviolin regulate synovial cell proliferation and apoptosis, at least in mice [11]. 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. Cloning of