Synoviolin/Hrd1, an E3 ubiquitin ligase, as a novel pathogenic factor for arthropathy
Synoviolin/Hrd1, an E3 ubiquitin ligase, as a novel pathogenic factor for arthropathy
复制标题
DOI：
10.1101/gad.1096603
复制
发表时间：
2003-10-01
影响因子：
10.5
通讯作者：
Nakajima, T
中科院分区：
文献类型：
--
作者：
Amano, T;Yamasaki, S;Nakajima, T
类风湿性关节炎（Rheumatoid arthritis，RA）是一种以滑膜增生为特征的严重关节疾病，严重影响患者的生活质量。然而，调节滑膜细胞生长的机制尚未完全了解。为了阐明其机制，我们利用抗类风湿滑膜细胞抗体进行免疫筛选，并鉴定和克隆了E3泛素连接酶“Synoviolin/Hrd 1”。Synoviolin/Hrd 1在类风湿性滑膜中高度表达，过表达该酶的小鼠出现自发性关节病。相反，滑膜细胞凋亡增强，滑膜细胞/hrd 1（+/-）小鼠对胶原诱导的关节炎有抵抗力。我们的结论是，Synoviolin/Hrd 1是一种新的关节病的致病因素，通过触发滑膜细胞生长，通过其抗凋亡作用。我们的研究结果提供了一个新的RA发病模型，并建议Synoviolin/Hrd 1可以作为RA的治疗策略。
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.