Mechanosensitive cation channel Piezo1 contributes to ventilator-induced lung injury by activating RhoA/ROCK1 in rats.

Abstract

BACKGROUND:

Mechanical ventilation can induce or aggravate lung injury, which is termed ventilator-induced lung injury (VILI). Piezo1 is a key element of the mechanotransduction process and can transduce mechanical signals into biological signals by mediating Ca2+ influx, which in turn regulates cytoskeletal remodeling and stress alterations. We hypothesized that it plays an important role in the occurrence of VILI, and investigated the underlying mechanisms.

METHODS:

High tidal volume mechanical ventilation and high magnitude cyclic stretch were performed on Sprague-Dawley rats, and A549 and human pulmonary microvascular endothelial cells, respectively, to establish VILI models. Immunohistochemical staining, flow cytometry, histological examination, enzyme-linked immunosorbent assay, western blotting, quantitative real-time polymerase chain reaction and survival curves were used to assess the effect of Piezo1 on induction of lung injury, as well as the signaling pathways involved.

RESULTS:

We observed that Piezo1 expression increased in the lungs after high tidal volume mechanical ventilation and in cyclic stretch-treated cells. Mechanistically, we observed the enhanced expression of RhoA/ROCK1 in both cyclic stretch and Yoda1-treated cells, while the deficiency or inhibition of Piezo1 dramatically antagonized RhoA/ROCK1 expression. Furthermore, blockade of RhoA/ROCK1 signaling using an inhibitor did not affect Piezo1 expression. GSMTx4 was used to inhibit Piezo1, which alleviated VILI-induced pathologic changes, water content and protein leakage in the lungs, and the induction of systemic inflammatory mediators, and improved the 7-day mortality rate in the model rats.

CONCLUSIONS:

These findings indicate that Piezo1 affects the development and progression of VILI through promotion of RhoA/ROCK1 signaling.

• Authors: Yang Zhang, Lulu Jiang, Tianfeng Huang, Dahao Lu, Yue Song, Lihui Wang, Ju Gao
• Journal: Respiratory research (Respir Res) Vol. 22 Issue 1 Pg. 250 (Sep 21 2021) ISSN: 1465-993X [Electronic] England
• PMID: 34548087 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s).

Chemical References

• Membrane Proteins
• Piezo1 protein, rat
• ROCK1 protein, rat
• rho-Associated Kinases
• RhoA protein, rat
• rho GTP-Binding Proteins

Topics

• A549 Cells
• Animals
• Humans
• Male
• Mechanotransduction, Cellular (physiology)
• Membrane Proteins (biosynthesis)
• Rats
• Rats, Sprague-Dawley
• Respiration, Artificial (adverse effects)
• Tidal Volume (physiology)
• Ventilator-Induced Lung Injury (metabolism, pathology)
• rho GTP-Binding Proteins (biosynthesis)
• rho-Associated Kinases (biosynthesis)