肝肺综合征（HPS）机制不明、防治困难，针对其核心进程“肺内微血管扩张（IPVD）”和新生血管生成机制进行研究一直是HPS防治研究策略。我们在前期研究工作中发现“CV-2/BMP2稳态失衡介导PMVECs肌样分化”是IPVD和新生血管生成病程中上游关键事件，值得深入研究。进一步预实验提示“棕榈酰转移酶DHHC24的过表达可能引起BMPR-II棕榈酰化修饰和细胞膜脂筏内外重分布，可能是导致 “CV-2/BMP2稳态”的主要原因。因此本课题拟建立HPS在体和PMVEC离体模型，采用基因转染、单分子荧光显微成像和质谱分析等技术，阐明DHHC24介导BMPR-II棕榈酰化修饰和胞膜重分布在CV-2/BMP2稳态失衡，继而导致PMVEC“肌样分化”中的作用，为制定以“BMPR-II棕榈酰化修饰和细胞膜脂筏内外重分布”为靶点，诱导恢复“CV-2/BMP2稳态”以获得更佳的HPS治疗新策略奠定理论基础。

Poorly defining the mechanisms responsible for the intrapulmonary microvascular dilation (IPVD) and neoangiogenesis result in no effective medical therapies of hepatopulmonary syndrome (HPS). Our previous study indicated that “the myogenic differentiation of PMVECs induced by CV-2/BMP2 imbalance” might be the key upsream event in the pathogenesis of IPVD and neoangiogenesis. Further, our preliminary experiments suggested that aberrant DHHC24 signaling leading to the lipid raft aggregation of BMPR-II and disorders of "CV-2/BMP2 homeostasis" could be the critical regulatory pathway. In this study, models of HPS and PMVECs will be established. Recombinant adenovirus transfection, total internal reflection fluorescence microscopy and mass spectrometry will be applied to identify the role of DHHC24/BMPR-II pathway regulating the myogenic differentiation of PMVECs in the pathogenesis of IPVD of HPS, to explore whether the regulation of DHHC24 activity inducts the maintenance of PMVECs differentiation is the more protective and new therapeatic strategies for HPS treatment.