Mechanosensitive Piezo Channels Modulate Airway Hyper-reactivity in a Mouse Model of Neonatal CPAP.

INTRODUCTION: Continuous positive airway pressure (CPAP) is a preferred respiratory support modality for preterm infants. Animal studies have shown long-term detrimental effects on lung/airway development such as airway hyper-reactivity (AHR) may be an unfortunate consequence of sustained stretch associated with neonatal CPAP. The objective of the present study is to investigate the role of the mechanosensitive Piezo2 (PZ2) channel as a potential mediator of AHR and airway smooth muscle morphology using our neonatal mouse model. METHODS: Neonatal mice were fitted with a custom-made mask for delivery of daily CPAP consisting of 3 h/day for 7 consecutive days. At postnatal day 21 (two weeks after CPAP ended), AHR and smooth muscle expression were assessed with and without modulation of PZ. RESULTS: CPAP-induced AHR was prevented by acute PZ2-specific and non-specific (PZ1 and PZ2) antagonist administration. AHR was associated with increased airway smooth muscle (ASM), which was reduced by siRNA treatment targeting PZ2. CONCLUSIONS: These data suggest the long-term effects of CPAP on airway function involve mechanosensitive PZ channels, which could contribute to wheezing disorders in former preterm infants who had received prior CPAP administration.