Mechanical strain-induced proliferation and signaling in pulmonary epithelial H441 cells.
Pulmonary epithelial cells are exposed to mechanical strain during physiological breathing and mechanical ventilation. Strain regulates pulmonary growth and development and is implicated in volutrauma-induced fibrosis. The mechanisms of strain-induced effects are not well understood. It was hypothesized that mechanical strain induces proliferation of pulmonary epithelial cells and that this is mediated by signals initiated within seconds of strain. To test this hypothesis, human pulmonary adenocarcinoma H441 cells were strained in vitro. Cyclic as well as tonic strain resulted in increased cellular proliferation. Western blot analysis of strained cells demonstrated three newly phosphorylated tyrosine residues within 30 s of strain. Phosphorylation of mitogen-activated protein kinases p42/44 increased, electrophoretic mobility shift assay demonstrated activation of transcription factor activating protein-1, and immunohistochemistry demonstrated increased phosphorylation of c-jun in response to strain. The tyrosine kinase inhibitor genistein blocked the strain-induced proliferation. We conclude that strain induces proliferation in pulmonary epithelial cells and that tyrosine kinase activity is necessary to signal the proliferative response to mechanical strain.
Chess
P R
PR
Department of Pediatrics, University of Rochester, Rochester, New York 14642, USA. patricia_chess@urmc.rochester.edu
Toia
L
L
Finkelstein
J N
JN
D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013314:Stress, Mechanical; D018808:Transcription Factor AP-1 / Q000502:physiology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D004791:Enzyme Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D014443:Tyrosine; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases