Inhibition of IP3R3 attenuates endothelial to mesenchymal transition induced by TGF-β1 through restoring mitochondrial function

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevated pulmonary artery pressure and right ventricular hypertrophy. Inositol 1,4,5-trisphosphate receptors (IP3Rs) release calcium ions from the endoplasmic reticulum to regulate permeability and migration of endothelial, thereby affecting PAH. In this study, We determined the expression level of IP3R3 and its position in lung tissue from PAH rat models, and stud the effect of IP3R3 on endothelial to mesenchymal transition (EndMT) and mitochondrial function of endothelial cells treated with TGF-β1. We observed that IP3R3 was significantly overexpressed in the lung tissues from PAH rat models. Inhibition of IP3R3 reduced EndMT markers, cell migration, ROS production, Ca2+ levels, increased mitochondrial membrane potential and mitochondrial respiratory chain complex I, III, and V activities. These results suggest that the inhibition of IP3R3 attenuated EndMT and migration induced by TGF-β1 via restoring of mitochondrial functions, thereby suggesting a novel therapeutic opportunity for PAH.