Deficiency of bone morphogenetic protein type II receptor (BMPRII) signaling has been implicated in the pathology of pulmonary arterial hypertension (PAH). Targeting BMPRII signaling with small molecular compound to selectively improve the function of the vascular endothelium could be a desirable therapeutic intervention for PAH.
To apply stem cell technology in drug discovery and identify BMPRII signalling regulators for the treatment of PAH.
Methods and Results
Because BMP2 has been reported to enhance endothelial BMPRII signaling, we screened 8 160 small molecular compounds for their potential as BMP2 upregulators. And we performed an assay on the BMPRII downstream gene Inhibitor of DNA binding 1 (Id1) using a dual reporter driven specifically in endothelial cells differentiated from human embryonic stem cells (hESCs-ECs). The identified leading compound restored BMPRII downstream signalling in human pulmonary arterial endothelium cells (hPAECs) and endothelial cells differentiated from PAH patients derived induced pluripotent stem cell (iPSCs-ECs).
Using stem cell technology, we gained a clearer understanding of the genetic cause of PAH and provided a potential drug screening method for cardiopulmonary disease.