Loss of lung microvascular endothelial Piezo2 expression impairs NO synthesis, induces EndMT, and is associated with pulmonary hypertension
Siyu Tian, Zongye Cai, Payel Sen, Denise van Uden, Esther van de Kamp, Raphaël Thuillet, Ly Tu, Christophe Guignabert, Karin A. Boomars, Kim van der Heiden, Maarten M. Brandt, Daphne Merkus
Abstract
The mechanosensory ion channel Piezo2 is exclusively expressed in lung microvascular endothelial cells (MVECs). Patient MVECs as well as animal models of pulmonary (arterial) hypertension showed lower expression of Piezo2 in the lung. Mechanistically, Piezo2 is required for calcium influx and NO production in response to shear stress, whereas stimuli known to induce endothelial to mesenchymal transition (EndMT) reduce Piezo2 expression in MVECs, and Piezo2 knockdown induces a gene and protein expression pattern consistent with EndMT.
Topics & Concepts
Gene knockdownLungCell biologyPulmonary hypertensionMedicineBiologyGeneCardiologyInternal medicineBiochemistryErythrocyte Function and PathophysiologyBlood properties and coagulationIon Transport and Channel Regulation