ChIP-chip of BMP2 or control treated human pulmonary artery endothelial cells with anti-beta-catenin or anti-ppar-gamma antibodies on promoter regions

Reduced bone morphogenetic protein receptor (BMPR)2 expression in patients with pulmonary arterial (PA) hypertension (PAH), can impair PA endothelial cell (EC) function. We now characterize, in human PAECs, a novel BMPR2-mediated transcriptionally active complex between peroxisome proliferator-activated receptor (PPAR) gamma and beta-catenin (BC), and show that disruption of this complex impairs BMP mediated HPAEC survival. Using whole genome wide ChIP-Chip promoter analysis we delineate PPARG-BC dependent transcription of target genes that include apelin. Comparison of ppar-gamma and beta-catenin occupancy on promoter regions from human pulmonary artery endothelial cells after either treatment with BMP2 (10ng/ml) or control. A total of 8 samples were created using NimbleGen human HG18 promoter arrays.

肺动脉高压（pulmonary arterial hypertension, PAH）患者体内骨形态发生蛋白受体2（bone morphogenetic protein receptor 2, BMPR2）表达水平降低，可损伤肺动脉内皮细胞（pulmonary arterial endothelial cell, EC）功能。本研究在人肺动脉内皮细胞（human pulmonary artery endothelial cells, PAEC）中鉴定出一种由BMPR2介导的、过氧化物酶体增殖物激活受体γ（peroxisome proliferator-activated receptor gamma, PPARγ）与β-连环蛋白（beta-catenin, BC）之间的新型转录活性复合物，并证实该复合物的破坏会削弱骨形态发生蛋白（bone morphogenetic protein, BMP）介导的人肺动脉内皮细胞（human pulmonary artery endothelial cells, HPAEC）存活能力。通过全基因组ChIP-Chip启动子分析，我们明确了依赖PPARγ-BC复合物的靶基因转录调控网络，其中包含Apelin。本研究对比了经BMP2（10ng/ml）处理与对照组处理后人肺动脉内皮细胞启动子区域的PPARγ与β-连环蛋白结合富集情况，共使用NimbleGen人类HG18启动子芯片构建了8个样本。