Bronchial epithelial compression regulates MAP kinase signaling and HB-EGF-like growth factor expression

Daniel J. Tschumperlin, Jonathan D. Shively, Melody A. Swartz, Eric S. Silverman, Kathleen J. Haley, Gerhard Raab, Jeffrey M. Drazen

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Airway smooth muscle constriction leads to the development of compressive stress on bronchial epithelial cells. Normal human bronchial epithelial cells exposed to an apical-to-basal transcellular pressure difference equivalent to the computed stress in the airway during bronchoconstriction demonstrate enhanced phosphorylation of extracellular signal-regulated kinase (ERK). The response is pressure dependent and rapid, with phosphorylation increasing 14-fold in 30 min, and selective, since p38 and c-Jun NH2-terminal kinase phosphorylation remains unchanged after pressure application. Transcellular pressure also elicits a ninefold increase in expression of mRNA encoding heparin-binding epidermal growth factor-like growth factor (HB-EGF) after 1 h, followed by prominent immunostaining for pro-HB-EGF after 6 h. Inhibition of the ERK pathway with PD-98059 results in a dose-dependent reduction in pressure-induced HB-EGF gene expression. The magnitude of the HB-EGF response to transcellular pressure and tumor necrosis factor (TNF)-α (1 ng/ ml) is similar, and the combined mechanical and inflammatory stimulus is more effective than either stimulus alone. These results demonstrate that compressive stress is a selective and potent activator of signal transduction and gene expression in bronchial epithelial cells.

Original languageEnglish (US)
Pages (from-to)L904-L911
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume282
Issue number5 26-5
DOIs
StatePublished - 2002

Keywords

  • Airway
  • Asthma
  • Mechanical stress
  • Mechanotransduction
  • Remodeling

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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