Bronchial epithelial compression regulates epidermal growth factor receptor family ligand expression in an autocrine manner

Eric K. Chu, John S. Foley, Jason Cheng, Anita S. Patel, Jeffrey M. Drazen, Daniel J. Tschumperlin

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

The epidermal growth factor receptor (ECFR), an important signaling pathway in airway biology, is stimulated by compressive stress applied to human airway epithelial cells. Although the EGFR ligand, heparin-binding epidermal growth factor-like growth factor (HB-ECF), is known to be released as a result of this stimulation, whether compressive stress enhances expression of other ECFR ligands, and the duration of mechanical compression required to initiate this response, is not known. Human airway epithelial cells were exposed to compressive stress, and expression of four ECFR ligands was examined by quantitative PCR. Cells were exposed to: (J) continuous compressive stress over 8 h, (2) compression with and without ECFR inhibitor (AC1478), or (3) time-limited compression (3.75, 7.5, 15, 30, and 60 min). Compressive stress produced a sustained upregulation of the ECFR ligands HB-ECF, epiregulin, and amphiregulin, but not transforming growth factor-α. Inhibition with AC1478 demonstrated that expression of HB-ECF, epiregulin, and amphiregulin is dependent on the signaling via the ECFR. Immunostaining for epiregulin protein demonstrated increased expression with compression and attenuation with ECFR inhibition. The response of all three ECFR ligands persisted long after the mechanical stimulus was removed. Taken together, these data suggest the possibility of a mechanically activated ECFR autocrine feedback loop involving selected ECFR ligands.

Original languageEnglish (US)
Pages (from-to)373-380
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume32
Issue number5
DOIs
StatePublished - May 2005

Keywords

  • Autocrine signaling, mechanical stress
  • Epidermal growth factor receptor
  • Epiregulin
  • Heparin-binding epidermal growth factor-like growth factor

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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