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.