Mechanosensitive ion channel Piezo1 mediates mechanical ventilation-exacerbated ARDS-associated pulmonary fibrosis

• DOI: 10.1016/j.jare.2022.12.006
• Publication Date: 2022-12-13T17:34:05Z
• Authors: Xiang-Zhi Fang; Min Li; Ya-Xin Wang; Pei Zhang; Miao-Miao Sun; Jia-Xin Xu; Yi-Yi Yang; Ya-Jun He; Yuan Yu; Rui-Ting Li; Ting Zhou; Le-Hao Reng; De-Yi Sun; Hua-Qing Shu; Shi-Ying Yuan; Ji-Qian Xu; You Shang
• Keywords: Piezo1

Pulmonary fibrosis is a major cause of the poor prognosis acute respiratory distress syndrome (ARDS). While mechanical ventilation (MV) an indispensable life-saving intervention for ARDS, it may remodeling process in lung epithelial cells to become disorganized and exacerbate ARDS-associated pulmonary fibrosis. Piezo1 mechanosensitive ion channel that known play role regulating diverse physiological processes, but whether necessary MV-exacerbated remains unknown.This study aimed explore fibrosis.Human were stimulated with hydrochloric acid (HCl) followed by stretch 48 h. A two-hitmodel MV afteracidaspiration-inducedlunginjuryin mice was used. Mice sacrificed after 14 days MV. Pharmacological inhibition knockout used delineate In some experiments, ATP or ATP-hydrolyzing enzyme apyrase administered.The stimulation human HCl resulted phenotypes epithelial-mesenchymal transition (EMT), which enhanced stretching. exacerbated exposed HCl. Pharmacologicalinhibitionorknockout attenuated EMT vivo vitro. Mechanistically, observed effects mediated Piezo1-dependent Ca2+ influx release cells.Our findings identify key increased cells. Inhibiting constitute novelstrategyfor treatment