Bronchial epithelial compression regulates MAP kinase signaling and HB-EGF-like growth factor expression.
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.
Published In/Presented At
Tschumperlin, D. J., Shively, J. D., Swartz, M. A., Silverman, E. S., Haley, K. J., Raab, G., & Drazen, J. M. (2002). Bronchial epithelial compression regulates MAP kinase signaling and HB-EGF-like growth factor expression. American journal of physiology. Lung cellular and molecular physiology, 282(5), L904–L911. https://doi.org/10.1152/ajplung.00270.2001
Medicine and Health Sciences
Department of Medicine