肺动脉高压是一种高发的致死性疾病，其发病机理不明。有研究提示缺氧诱导丝裂原因子(HIMF)诱导肺动脉脉高压的产生，其机制可能是通过和细胞膜外受体结合，但该受体的分子本质一直未阐明，申请人已有研究已证实HIMF通过和细胞膜钙感受器(CaSR)的胞内段结合参与慢性缺氧性肺动脉高压的发生。申请人围绕本项目开展预实验发现在慢性缺氧性肺动脉高压大鼠肺组织中HIMF和细胞膜上受体骨形态发生蛋白2型受体(BMPR2)存在相互作用，据此本项目推测：慢性缺氧时HIMF可能通过和膜上受体BMPR2的胞外段结合抑制BMPR2的活性导致肺动脉高压的发生。为此，本研究采用慢性缺氧肺动脉高压模型，研究HIMF与BMPR2在肺动脉高压中的相互作用及影响，并进一步利用酵母双杂交技术等手段筛查两者结合关键的氨基酸序列并进行靶向突变干预，为阐明肺动脉高压发生原理提供新的依据，并为靶向治疗肺动脉高压提供新的研究方向。

Pulmonary arterial hypertension is a high incidence of fatal disease which pathogenesis unknown . Studies have shown that hypoxia-induced mitogenic factor (HIMF) can induce pulmonary arterial hypertension by activating a membrane receptor, but the idendity of the membrane receptor remains unkownn.The applicant have confirmed that HIMF promoted the occurrence of chronic hypoxic pulmonary hypertension thought interacting with the intracellular segment of CaSR . The applicant carried out the preliminary expriment and found that HIMF interactions with the membrane receptor of bone morphogenetic protein 2 receptor (BMPR2) in the rat lung tissue with chronic hypoxic pulmonary hypertension. The project hypothesizes that HIMF may bind to the extracellular BMPR2 and suppress the activity of BMPR2 and thus participate in the occurrence of chronic hypoxic pulmonary hypertension. This project will further elucidate the interaction between HIMF and BMPR2 and the influence in pulmonary arterial hypertension using the classic animal model of chronic hypoxic pulmonary hypertension, and disrupting the key amino acid sites which the HIMF and BMPR2 interaction screened by yeast-two-hybrid technique，This project is going to llustrate a new theroy for the occurrence of pulmonary hypertension and provide new research direction for targeted treatment of pulmonary hypertension.