Mechanical stretch induces lung α-epithelial Na+channel expression

Shamimunisa B. Mustafa, John Isaac, Steven R. Seidner, Patricia S. Dixon, Barbara M. Henson, Robert J. Digeronimo

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)380-391
Number of pages12
JournalExperimental Lung Research
Volume40
Issue number8
DOIs
Publication statusPublished - Oct 1 2014

    Fingerprint

Keywords

  • Cyclic stretch
  • Epithelial cells
  • Lung
  • MAP kinase
  • Sodium channels

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry

Cite this

Mustafa, S. B., Isaac, J., Seidner, S. R., Dixon, P. S., Henson, B. M., & Digeronimo, R. J. (2014). Mechanical stretch induces lung α-epithelial Na+channel expression. Experimental Lung Research, 40(8), 380-391. https://doi.org/10.3109/01902148.2014.934410