Apical and basolateral EGF receptors regulate gastric mucosal paracellular permeability

Monica C. Chen, Jeffrey Goliger, Nigel Bunnett, Andrew H. Soll

Research output: Contribution to journalArticlepeer-review

Abstract

Previous studies found that monolayers formed from canine oxyntic epithelial cells in primary culture displayed remarkable resistance to apical acidification and both mitogenic and migratory responses to epidermal growth factor (EGF) treatment. In our present studies, we found that EGF increased transepithelial resistance (TER) but not short-circuit current in these monolayers. Parallel effects of EGF on decreasing mannitol flux and increasing TER implicate direct regulation of paracellular permeability. EGF acting at either apical and basolateral receptors rapidly increased TER, but the apical response was sustained whereas the basolateral response was transient. 125I-labeled EGF binding revealed specific apical binding, but receptor numbers were 25-fold lower than on the basolateral surface. Both apical and basolateral EGF activated tyrosine phosphorylation of EGF receptors (EGFR), β-catenin, and cellular substrate as evident on confocal microscopy. Although apical EGF activated a lesser degree of receptor autophosphorylation than basolateral EGF, phosphorylation of β-catenin was equally prominent with apical and basolateral receptor activation. Together, these findings indicate that functional apical and basolateral EGFR exist on primary canine gastric epithelial cells and that these receptors regulate paracellular permeability. The sustained effect of apical EGFR activation and prominent phosphorylation of β-catenin suggest that apical EGFR may play a key role in this regulation.

Original languageEnglish (US)
Pages (from-to)G264-G272
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume280
Issue number2 43-2
DOIs
StatePublished - Feb 2001

Keywords

  • Epidermal growth factor receptors
  • Gastric mucosal defense
  • Paracellular pathway
  • Transforming growth factor receptors

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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