title: Mechanical stretch induces lung α-epithelial Na(+) channel expression.
abstract: ABSTRACT During fetal development physiological stretching helps drive lung growth and maturation. At birth, the α-subunit of the alveolar epithelial sodium channel (α-ENaC) is a critical factor in helping to facilitate clearance of lung fluid during the perinatal period. The effects of stretch, however, on α-ENaC expression in the fetal lung have yet to be elucidated. In an effort to explore this question, we used both an in vitro cell culture model that exposes cells to repetitive cyclic stretch (CS) as well as an in vivo preterm animal model of mechanical ventilation (MV). We found that murine lung epithelial (MLE-12) cells exposed to repetitive CS showed a significant rise in α-ENaC mRNA expression. Total and cell-surface protein abundance of α-ENaC were also elevated after 24 h of CS. Stretch-induced increases in α-ENaC expression were suppressed in the presence of either actinomycin D or cycloheximide. Pharmacological inhibition of the extracellular signal-regulated protein kinase (ERK1/2) did not attenuate stretch-induced increases in α-ENaC protein, whereas inhibition of p38 MAPK or c-Jun NH2-terminal kinase (JNK) did. In 29-day preterm rabbits, alveolar stretching secondary to postnatal MV markedly elevated fetal lung α-ENaC expression compared to spontaneously breathing counterparts. In summary, our findings indicate that mechanical stretch promotes α-ENaC expression.
authors: 1Department of Pediatrics, University of Texas Health Science Center , San Antonio Texas , USA.
authors: Shamimunisa B
authors: SB
authors: Mustafa
authors: John
authors: J
authors: Isaac
authors: Steven R
authors: SR
authors: Seidner
authors: Patricia S
authors: PS
authors: Dixon
authors: Barbara M
authors: BM
authors: Henson
authors: Robert J
authors: RJ
authors: DiGeronimo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D005260:Female; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011247:Pregnancy; D011817:Rabbits; D011897:Random Allocation; D020545:Respiratory Mucosa / Q000378:metabolism*; D013314:Stress, Mechanical
chemical_list: D053503:Epithelial Sodium Channels; D020928:Mitogen-Activated Protein Kinases
keywords: MAP kinase; cyclic stretch; epithelial cells; lung; sodium channels