Effect of mechanosensor channel Piezo1 on alveolar epithelial barrier function and wound healing

<bold>Background:</bold> Piezo1, a mechanosensitive and non-selective cation channel, performs an essential function in several physiological processes. However, little is known about their effects on the barrier function and wound-healing of the alveolar epithelium. <bold>Aims and Objectives:</bold> To investigate the effect of Piezo1 on the pathogenesis of acute lung injury, especially alveolar epithelial barrier dysfunction and the wound healing. <bold>Methods:</bold> Rat type II alveolar epithelial cells were isolated from 5-6 week-old male Sprague Dawley rats. To estimate barrier function, the cells were seeded onto collagen-coated transwells and transdifferentiated into type I-like cells to make confluent monolayer. The monolayer was stimulated with tumor necrosis factor alpha (TNFα), dexamethasone, and grammostola spatulata mechanotoxin 4 (GsMTx4), a Piezo1 receptor antagonist. Barrier function was evaluated by trans-epithelial electrical resistance (TEER). Areas of wound made by the scratching of type I-like cells monolayer with pipet tips were measured at 0 and 16 hours after stimulation. <bold>Results:</bold> GsMTx4 (10 μg/mL) did not affect barrier function in intact or damaged alveolar epithelial cell monolayer in the absence or presence of TNFa (10 ng/mL, p=0.16 and p=0.16, respectively). On the other hand, GsMTx4 accelerated repair of scratch wounds (p=0.02). Dexamethasone (100 nM) delayed wound repair, which was significantly recovered by GsMTx4 (p=0.009). <bold>Conclusion:</bold> Piezo1 has no effects on alveolar epithelial barrier function, whereas its inhibition improves dexamethasone-induced delay of alveolar epithelium wound-healing.