系统性硬化症（systemic sclerosis, SSc）是一种慢性、进行性自身免疫性疾病，临床上以皮肤增厚和纤维化、血管损害以及内脏受累为特征，常发生心、肺、肾等重要脏器损害，最终导致死亡。血管病变是SSc预后极差的主要因素。SSc的血管损害机制迄今未明，补体C3片断C3f和去精氨酸C3f（DRC3f）是补体活化过程中C3b失活所产生的多肽片段，我们的前期研究显示它们在诱导SSc的血管内皮细胞增殖中起重要作用。为进一步探讨其分子学作用机制，我们拟采用蛋白质谱分析结合表面等离子共振技术对其结合的靶分子进行分析，并通过信号通路分析对其诱发的细胞内转导信号进行研究，进而探讨调控靶分子表达和抑制信号通路在预防C3f和DRC3f介导的血管内皮细胞增生中的作用，为深入了解SSc血管病变的机制，及为临床上寻找预防和控制SSc血管病变的新靶向治疗提供实验室依据。

Systemic sclerosis (SSc) is a chronic progressive autoimmune disease characterized as pachyderma, fibrosis, vessel damage and organ involvement including progressive impairment of heart, lung and kidney, and finally leading to death. Over proliferation of vascular endothelial cell is considered the basic pathologic factor of fatal vasculopathy in patients with SSc. However, the mechanism of SSc remains unknown. Recently, our study found that complement C3 fragment des-arginine C3f (DRC3f), a small peptide with 16 amino acid removed arginine by carboxypeptidase from C3f, dramatically increased in sera of patients with SSc, and further investigation demonstrated that DRC3f and its former molecule C3f, derived from inactivation of C3b by I Factor, enhanced proliferation of vascular endothelial cell in vitro. This phenomenon suggested that C3f/DRC3f might be involved in the pathologic course of SSc by combining with the target molecule on or in the endothelial cell and resulting in a series of biological responses. THe purpose of this study will try to find out the target molecule of C3f/DRC3f in endothelial cell membrane proteins and to demonstrate the signal conduction in the cell activated by combining of C3f/DRC3f and its target molecule, and finally to investigate the preventive effect of C3f/DRC3f-induced proliferation of vascular endothelial cell by inhibition of target molecule expression or signal conduction in the cell. These results would be helpful for us to make clear the mechanism of SSc vasculopathy and to offer the experimentary evidence for the new targeted therapy of prevention and control of SSc vasculopathy.