ADGRG6/GPR126 as a Novel Therapeutic Target in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a chronic and fatal disease of the lungs. The 3‐year survival rate is 50–60%, as current therapies of PAH have limited effect on mortality. An important feature of PAH is the increased proliferation and contractile activity of pulmonary arterial smooth muscle cells (PASMCs). We cultured patient‐derived PASMCs and performed RNA‐seq on PASMCs from control and PAH lungs. We found that the expression of a G protein‐coupled receptor (GPCR) ADGRG6 (adhesion GPCR G6, or GPR126) is ~10‐fold higher in PAH patient PASMCs compared to control PASMCs. To test its functional activity, we overexpressed ADRGR6 in HEK293 cells, and found that proliferation of the cells decreased by 60% at 48 hours after transfection. Using qPCR, we observed that expression of cell cycle/proliferation markers CDK1, CDK2, and MKI67 was decreased after 48 hours, while expression of apoptosis markers VIM, ITGAM, and PCDH7 was increased. Additional preliminary data using flow cytometry indicate that cells overexpressing ADGRG6 are stalled at the S/G2 cell cycle checkpoint. These data suggest that ADRGRG6 activation could cause reduced proliferation in smooth muscle cells and be a viable target for PAH therapy. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .