血管钙化类似成骨矿化过程，是类风湿关节炎（RA）中膜钙化的病理基础，是患者死亡的重要危险因子，炎症因子以不同方式参与其中，机制不明。我们早已证实RA体内异常高表达的IL-29具有较强促炎作用且损伤血管内皮功能。新近发现RA患者血清IL-29含量与冠状动脉钙化显著相关，小鼠钙化血管异常高表达IL-29特异受体IL-28Rα，IL-29激活血管平滑肌细胞(VSMC)stat3通路诱导钙化标志基因BMP2表达。基于工作基础和最新发现，提出假说：RA体内促炎因子IL-29与VSMC表面受体IL-28Rα结合，激活stat3，促进BMP2基因表达，加重血管钙化。将利用Cas9活体编辑小鼠、血管钙化及关节炎小鼠，MicroCT、转染、细胞3D培养、CHIP、Luciferase及阻断等技术系统研究IL-29在RA血管钙化中的作用及机制，有助于发现IL-29作用新机制及临床RA血管钙化防治新靶点。

Vascular calcification resembling osteogenic mineralization is a pathologic foundation of medial calcification in rheumatoid arthritis and a strong risk marker for the mortality in RA patients, in which inflammatory cytokines might affect the process of vascular calcification in different manners, however, the underlying mechanism remains unknown. We previously reported that IL-29 is a strong proinflammatory cytokine to promote synovial inflammation and endothelial dysfunction during RA pathogenesis. On the basis of our preliminary results that IL-29 concentration in sera was associated with increased coronary artery calcium in RA patients, and the expression of IL-28Ra (the specific receptor of IL-29) was significantly elevated in calcified aortic tissues of mice, furthermore, IL-29 induced stat3 activation and increased BMP2 expression in VSMC cells. We therefore hypothesized IL-29 can accelerate vascular calcification in RA by promotion of VSMC osteogenic mineralization and calcification through regulating stat3/BMP2 signal pathway. In the study, we will employ CRISP/cas9 knock in/out mice, vascular calcified mice and arthritic mice, MicroCT, transfection, 3D cell culture, luciferase reporter detection and blocking techniques to investigate the effect and mechanism of IL-29 on RA vascular calcification. Our results will contribute to reveal the new mechanism of IL-29 action and deeply find a new target for prevention and cure of vascular calcification in RA disease.