Transcriptional analysis of the impact of BMPR2 loss and BMP9 treatment on pulmonary artery endothelial cells

Pulmonary arterial hypertension (PAH) is a disease of the pulmonary endothelium associated with mutations in BMPR2, the gene encoding the bone morphogenetic protein (BMP) type II receptor (BMPR-II). Loss of BMPR-II in the pulmonary endothelium has been shown to alter the functional response of the endothelium to BMP9 treatment from growth suppression in healthy cells, to hyperproliferation with the loss of BMPR-II. To investigate the molecular mechanisms underlying this phenotypic switch, we performed RNA sequencing on total RNA isolated from primary human pulmonary artery endothelial cells treated with or without BMP9 following BMPR2 knockdown or control. To investigate the role of BMPR2 loss and BMP9 treatment in the pulmonary endothelium, primary human pulmonary artery endothelial cells (HPAECs) were treated with or without 1ng/mL of BMP9 for 24 hours following the siRNA mediated knockdown of BMPR2 or control siRNA treatment.

肺动脉高压（PAH）是一类与BMPR2基因突变相关的肺内皮疾病，BMPR2即编码骨形态发生蛋白（BMP）II型受体（BMPR-II）的基因。已有研究证实，肺内皮中BMPR-II的缺失会改变内皮细胞对BMP9处理的功能响应：健康细胞的响应为生长抑制，而在BMPR-II缺失的细胞中则转变为过度增殖。为探究该表型转换背后的分子机制，我们对经BMPR2敲低或对照处理、随后接受或未接受BMP9处理的人原代肺动脉内皮细胞的总RNA进行了RNA测序。为明确BMPR2缺失与BMP9处理在肺内皮中的作用，我们先对人原代肺动脉内皮细胞（HPAECs）进行BMPR2的小干扰RNA（siRNA）介导敲低或对照siRNA处理，随后以1ng/mL浓度的BMP9处理24小时，部分细胞未接受BMP9处理。