Id蛋白调节肺动脉高压血管重构及肺动脉平滑肌细胞增殖的机制研究

Vascular remodeling is one of pathological characteristics of Pulmonary Arterial Hypertension (PAH) while over proliferation of Pulmonary Arterial smooth muscle cells(PASMCs) is a key reason for vascular remodeling. Bone morphogenetic proteins receptor 2 (BMPR2) gene mutations and dysfunction of BMP signaling pathway are closely related to various types of PAH, and BMP signaling pathway play a key role on the regulation of PASMCs proliferation and vessel homeostasis, but the underlying mechanism is seldom known.Our previously work has found that the expression of Id proteins,which are the main downstream protein of BMP signaling pathways, is strongly regulated by BMPR2 in PASMCs, while Id1 and Id3 may be the main proteins mediating BMP's funtion on PASMCs proliferation.With animal model and molecular biology technique,the present study is designed to investigate the crucial role of Id proteins in regulating PASMCs proliferation and vascular remodeling in PAH. Furthermore,we are also aim to uncover the underlying mechanism and reveal that if this process involve the cell cycle related protein, including CDK,p21 and so on. Our results will be helpful to reveal the pathogenesis of PAH and afford new evidences for searching new target in treatment and prevention of PAH.

血管重构是肺动脉高压（Pulmonary Arterial Hypertension, PAH）主要病理特征之一，肺动脉平滑肌细胞（PASMCs）过度增殖是引起肺血管重构的关键原因。骨形成蛋白受体2(BMPR2)基因突变，BMP信号通路受损与多种类型肺动脉高压的发生发展密切相关，对调节肺血管稳态特别是PASMCs增殖起着关键作用，但其机制尚不明确。本项目预实验及所在实验室前期研究发现，Id蛋白作为BMP信号通路主要下游蛋白，其在肺动脉平滑肌细胞的表达受BMPR2的调控，其中Id1与Id3可能为介导BMP调节PASMCs增殖作用的主要蛋白。本研究将从动物模型和细胞分子水平探讨Id蛋白在介导肺动脉高压血管重构和PASMCs增殖中的作用，进一步揭示其调节机制是否与调节细胞周期相关蛋白CDK、p21等有关。研究结果将有助于揭示肺动脉高压发病机制，为寻找新的肺动脉高压防治靶点提供实验依据。

血管重构是肺动脉高压（Pulmonary Arterial Hypertension, PAH）主要病理特征之一，肺动脉平滑肌细胞（PASMCs）过度增殖是引起肺血管重构的关键原因。骨形成蛋白受体2(BMPR2)基因突变，BMP信号通路受损与多种类型肺动脉高压的发生发展密切相关，对调节肺血管稳态特别是PASMCs增殖起着关键作用，但其机制尚不明确。本研究将从动物模型和细胞分子水平探讨Id蛋白在介导肺动脉高压血管重构和PASMCs增殖中的作用。本项目主要研究发现有两点：第一是确证Id蛋白作为BMP信号通路下游关键分子在肺动脉高压大鼠血管重构与PASMCs增殖中的主要调控作用，其中Id1与Id3发挥重要作用；第二是阐明Id蛋白在调节肺血管重构与PASMCs增殖中的作用机制，确定其与细胞周期相关蛋白如篇p21等有关。项目按照计划实施，取得了预期结果。