Piezo channels in stretch effects on developing human airway smooth muscle

Area of Science:

• Pulmonary Medicine
• Cell Biology
• Neonatology

Background:

• Respiratory support, like continuous positive airway pressure (CPAP), can overstretch premature infants' airways.
• This mechanical stress may lead to long-term airway hyperreactivity and remodeling, but the underlying mechanisms are unclear.
• Airway smooth muscle cells are crucial for airway contractility and remodeling.

Purpose of the Study:

• To investigate the role of mechanosensitive Piezo (PZ) channels in detrimental airway responses to stretch in developing airways.
• To determine if PZ channels are expressed and functional in human fetal airway smooth muscle (fASM) cells.

Main Methods:

• Utilized 18-22-week gestation human fetal airway smooth muscle (fASM) cells as an in vitro model.
• Assessed the expression of PZ1 and PZ2 channels under varying stretch conditions.
• Measured intracellular calcium ([Ca2+]i) responses and extracellular matrix (ECM) production following PZ channel activation (Yoda1 or stretch).

Main Results:

• PZ1 and PZ2 channels are expressed in developing airway smooth muscle and their expression is modulated by mechanical stretch.
• Activation of PZ channels by Yoda1 or stretch significantly increased intracellular calcium levels.
• Stretch-induced PZ channel activation led to increased extracellular matrix production.

Conclusions:

• Functional Piezo channels are present in the developing airway smooth muscle.
• These channels contribute to intracellular calcium signaling and extracellular matrix remodeling in response to mechanical stretch.
• Findings suggest Piezo channels may mediate detrimental airway changes in preterm infants receiving respiratory support, potentially contributing to chronic airway diseases.