Endothelial Upregulation of Mechanosensitive Channel Piezo1 in Pulmonary Hypertension
Am J Physiol Cell Physiol. 2021 Oct 20. doi: 10.1152/ajpcell.00147.2021. Online ahead of print.ABSTRACTPiezo is a mechanosensitive cation channel responsible for stretch-mediated Ca2+ and Na+ influx in multiple types of cells. Little is known about the functional role of Piezo1 in the lung vasculature and its potential pathogenic role in pulmonary arterial hypertension (PAH). Pulmonary arterial endothelial cells (PAECs) are constantly under mechanic stretch and shear stress that are sufficient to activate Piezo channels. Here we report that Piezo1 is significantly upregulated in PAECs from patients with idiopathic PAH and animals with experimental pulmonary hypertension (PH) compared to normal controls. Membrane stretch by decreasing extracellular osmotic pressure or by cyclic stretch (18% CS) increases Ca2+-dependent phosphorylation (p) of AKT and ERK, and subsequently upregulates expression of Notch ligands, Jagged1/2 (Jag1 and Jag-2), and Delta like-4 (DLL4) in PAECs. siRNA-mediated downregulation of Piezo1 significantly inhibited the stretch-mediated pAKT increase and Jag-1 upregulation, while downregulation of AKT by siRNA markedly attenuated the stretch-mediated Jag1 upregulation in human PAECs. Furthermore, the mRNA and protein expression level of Piezo1 in the isolated pulmonary artery, which mainly contains pulmonary arterial smooth muscle cells (PASMCs), from animals with severe PH was also significantly higher than that from control animals. Taken together, our stu...
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Ziyi Wang Jiyuan Chen Aleksandra Babicheva Pritesh P Jain Marisela Rodriguez Ramon J Ayon Keeley S Ravellette Linda Wu Francesca Balistrieri Haiyang Tang Xiaomin Wu Tengteng Zhao Stephen M Black Ankit A Desai Joe G N Garcia Xin Sun John Y-J Shyy Daniela V Source Type: research