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

Am J Physiol Lung Cell Mol Physiol. 2002 May;282(5):L904-11. doi: 10.1152/ajplung.00270.2001.


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 NH(2)-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)-alpha (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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bronchi / cytology
  • Cells, Cultured
  • Compressive Strength
  • Enzyme Inhibitors / pharmacology
  • Epidermal Growth Factor / genetics*
  • Epidermal Growth Factor / metabolism
  • Flavonoids / pharmacology
  • Gene Expression / physiology
  • Heparin-binding EGF-like Growth Factor
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • MAP Kinase Signaling System / physiology*
  • Mitogen-Activated Protein Kinases / metabolism
  • Osmotic Pressure
  • Phosphorylation
  • RNA, Messenger / analysis
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / metabolism*


  • Enzyme Inhibitors
  • Flavonoids
  • HBEGF protein, human
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Epidermal Growth Factor
  • Mitogen-Activated Protein Kinases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one