2. Academic Validation
  3. Mechanosensitive ion channel Piezo1 mediates mechanical ventilation-exacerbated ARDS-associated pulmonary fibrosis

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

  • J Adv Res. 2022 Dec 13;S2090-1232(22)00285-5. doi: 10.1016/j.jare.2022.12.006.
Xiang-Zhi Fang 1,  Min Li 2,  Ya-Xin Wang 1,  Pei Zhang 3,  Miao-Miao Sun 4,  Jia-Xin Xu 1,  Yi-Yi Yang 4,  Ya-Jun He 1,  Yuan Yu 1,  Rui-Ting Li 1,  Ting Zhou 1,  Le-Hao Reng 1,  De-Yi Sun 1,  Hua-Qing Shu 1,  Shi-Ying Yuan 1,  Ji-Qian Xu 5,  You Shang 6
Affiliations

Affiliations

  • 1 Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Department of Pain Management, Wuhan No. 1 Hospital, Wuhan, Hubei Province, China.
  • 3 Department of Paediatrics, Jinling Hospital, School of Medicine, Nanjing University, China.
  • 4 Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 5 Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: xjq5456.good@163.com.
  • 6 Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: you_shanghust@163.com.
PMID: 36526145 DOI: 10.1016/j.jare.2022.12.006
Abstract

Introduction: Pulmonary fibrosis is a major cause of the poor prognosis of acute respiratory distress syndrome (ARDS). While mechanical ventilation (MV) is an indispensable life-saving intervention for ARDS, it may cause the remodeling process in lung epithelial cells to become disorganized and exacerbate ARDS-associated pulmonary fibrosis. Piezo1 is a mechanosensitive ion channel that is known to play a role in regulating diverse physiological processes, but whether Piezo1 is necessary for MV-exacerbated ARDS-associated pulmonary fibrosis remains unknown.

Objectives: This study aimed to explore the role of Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis.

Methods: Human lung epithelial cells were stimulated with hydrochloric acid (HCl) followed by mechanical stretch for 48 h. A two-hitmodel of MV afteracidaspiration-inducedlunginjuryin mice was used. Mice were sacrificed after 14 days of MV. Pharmacological inhibition and knockout of Piezo1 were used to delineate the role of Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis. In some experiments, ATP or the ATP-hydrolyzing Enzyme apyrase was administered.

Results: The stimulation of human lung epithelial cells to HCl resulted in phenotypes of epithelial-mesenchymal transition (EMT), which were enhanced by mechanical stretching. MV exacerbated pulmonary fibrosis in mice exposed to HCl. Pharmacologicalinhibitionorknockout of Piezo1 attenuated the MV-exacerbated EMT process and lung fibrosis in vivo and in vitro. Mechanistically, the observed effects were mediated by Piezo1-dependent CA2+ influx and ATP release in lung epithelial cells.

Conclusions: Our findings identify a key role for Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis that is mediated by increased ATP release in lung epithelial cells. Inhibiting Piezo1 may constitute a novelstrategyfor the treatment of MV-exacerbated ARDS-associated pulmonary fibrosis.

Keywords

Acute respiratory distress syndrome; Mechanical ventilation; Piezo1; Pulmonary fibrosis.

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