系统性硬化症(SSc)发病机制不清。内皮祖细胞（EPC）及间充质干细胞(MSC)功能障碍是SSc血管生成障碍的基础。内皮细胞损伤和活化是SSc发病机制中关键环节。连接粘附分子A（JAM-A）被证明在血管生成中起重要作用。我们既往研究发现SSc皮肤血管内皮细胞JAM-A表达减少；SSc患者血清JAM-A升高，患者EPC中JAM-A表达减少。我们推断JAM-A在SSc发病机制特别是内皮细胞障碍中起重要作用。我们将研究SSc患者在MSC、EPC、循环内皮细胞（CEC）与正常人的区别；MSC、EPC向内皮细胞转化障碍；JAM-A在其中的作用。研究患者MSC、EPC、CEC与甲褶微循环检查等血管障碍相关临床实验室指标的关系；JAM-A与它们的相关性。最后通过博来霉素诱导的硬皮病的模型来验证阻断JAM-A对皮肤纤维化、肺间质纤维化、内皮障碍等方面的影响，从而明确JAM-A在硬皮病发病机制中的作用。

The pathogenesis of systemic sclerosis (SSc) is unclear.Functional defects of endothelial progenitor cells (EPCs), as well as mesenchymal stem cells (MSCs) might be the basis of impaired angiogenesis in SSc. Endothelial cell injury and activation is key in the pathogenesis of SSc. Junctional adhesion molecule A(JAM-A) has been shown to play important role in angiogenesis.We had demonstrated decreasing expression of JAM-A in SSc skin endothelial cells and increasing JAM-A in SSc serum. SSc patients EPCs JAM-A expression were lower. We assume that JAM-A plays important role in pathogenesis of SSc especially in endothelial cells dysfunction. We will study the difference between the SSc patients and normal person in MSC, EPC, the circulating endothelial cells (CEC); EPC and MSC abnormality in endothelial cells formation; what’s JAM-A role in it. We’ll study the relationship between MSC、EPC、CEC and clinical laboratory examination such as Nailfold Videocapillaroscopy; what’s JAM-A role in it. Finally we use bleomycin-induced scleroderma mice to verify the blocking JAM - A roles in such as skin fibrosis, pulmonary fibrosis, endothelial dysfunction and to understand the JAM - A role in the pathogenesis of scleroderma.