The transcriptional regulation of Synoviolin in rheumatoid synovial cells.

类风湿性关节炎（RA）显著影响生活质量。我们最近克隆了一种与内质网相关降解（ERAD）途径有关的环型e3泛素连接酶synoviolin。滑膜因子在类风湿滑膜细胞中高度表达，可能参与RA的发病机制。在本研究中，我们发现ILF-3与GABPα在类风湿滑膜细胞中上调滑膜的表达。此外，我们证明滑膜鞘不仅参与RA的发病，还参与肝纤维化的发展。抑制滑膜活动是治疗类风湿性关节炎的一种潜在有效的治疗方法。我们最近发现了两类抑制滑膜小提琴活动的小分子。这些抑制剂抑制类风湿滑膜细胞的增殖，并在RA小鼠模型中显著降低疾病的严重程度。我们的研究结果表明，抑制滑膜鞘是治疗类风湿性关节炎的一种潜在的有效方法。

Rheumatoid arthritis(RA) significantly affects quality of life. We recently cloned synoviolin, a RING-typeE3 ubiquitin ligase implicated in the endoplasmic reticulum-associated degradation(ERAD) pathway. Synoviolin is highly expressed in rheumatoid synovial cells and may be involved in the pathogenesis of RA. In this study, we found that ILF-3 up-regulates synoviolin expression with GABPα in rheumatoid synovial cells. Moreover, we demonstrated that Synoviolin is involved in not only onset of RA but also development of liver fibrosis. Inhibition of synoviolin activity is a potentially useful therapeutic approach for the treatment of RA. We recently identified two classes of small molecules which inhibited synoviolin activity. These inhibitors suppressed the proliferation of rheumatoid synovial cells, and significantly reduced the severity of disease in a mouse model of RA. Our results suggest that inhibition of synoviolin is a potentially useful approach in the treatment of RA.