Mechanical stretch induces lung α-epithelial Na(+) channel expression

Area of Science:

• Pulmonary Physiology
• Molecular Biology
• Developmental Biology

Background:

• Physiological stretching is vital for fetal lung growth and maturation.
• Alpha-ENaC (α-ENaC) is critical for perinatal lung fluid clearance.
• The impact of stretch on fetal lung α-ENaC expression remains unclear.

Purpose of the Study:

• To investigate the effects of mechanical stretch on α-ENaC expression in fetal lung development.
• To elucidate the molecular mechanisms underlying stretch-induced α-ENaC regulation.
• To validate findings in both in vitro and in vivo models.

Main Methods:

• In vitro: Murine lung epithelial cells (MLE-12) subjected to cyclic stretch (CS).
• In vivo: Preterm rabbit model with mechanical ventilation (MV).
• Analysis of α-ENaC mRNA and protein levels, and involvement of signaling pathways (ERK1/2, p38 MAPK, JNK).

Main Results:

• Cyclic stretch significantly increased α-ENaC mRNA and protein expression in MLE-12 cells.
• Stretch-induced α-ENaC upregulation was dependent on transcription and translation.
• Inhibition of p38 MAPK and JNK, but not ERK1/2, attenuated stretch-induced α-ENaC.
• Postnatal mechanical ventilation in preterm rabbits elevated fetal lung α-ENaC expression.

Conclusions:

• Mechanical stretch promotes α-ENaC expression in the developing lung.
• The p38 MAPK and JNK pathways are involved in mediating stretch-induced α-ENaC upregulation.
• Findings highlight the role of mechanical forces in regulating key ion channels for lung function.