Apical EGF receptors regulate epithelial barrier to gastric acid: endogenous TGF-α is an essential facilitator

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 46; no. 5; pp. G1098 - G1106
• Main Authors: CHEN, Monica C, SOLOMON, Travis E, KUI, Robert, SOLL, Andrew H
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Physiological Society 01.11.2002
• Subjects: Acids; Anatomy & physiology; Biological and medical sciences; Digestive system; Fundamental and applied biological sciences. Psychology; Stomach; Ulcers; Vertebrates: digestive system; Fissipedia; Stomach; Carnivora; Glandular cell; Digestive system; Electrophysiology; Cell junction; In vitro; Apical membrane; Cell orientation; Vertebrata; Transepithelial potential; Mammalia; Epidermal growth factor; Monolayer culture; Animal; Primary culture; Epithelial cell; Tight junction; Transforming growth factor α; Dog; Permeability barrier; Biological receptor
• ISSN: 0193-1857; 1522-1547

In previous studies, we found that apical and basolateral EGF receptors (EGFR) on primary canine gastric monolayers decreased paracellular permeability, evident by increased transepithelial electrical resistance (TER) and decreased flux of [3H]mannitol (MF). After studying monolayers in Ussing chambers, we now report that treatment with apical, but not basolateral, EGF enhanced tolerance to apical H+, evident by a slower decay in TER and an attenuated rise in MF. Enhanced tolerance to apical acid was evident within 10 min of treatment with apical EGF. Immunoneutralization of endogenous transforming growth factor (TGF)- accelerated the drop in TER and the rise in MF in response to apical acidification; apical EGF reversed these effects. Study of monolayers cultured in Transwell inserts showed that immunoblockade of basolateral, but not apical, EGFR also impaired the resistance to apical acidification and enhanced MF. We conclude that apical EGFR regulates the barrier to apical acidification via effects on paracellular resistance. Although exogenous basolateral EGF has a less apparent effect on the barrier to acid, endogenous ligand active at basolateral EGFR plays an important role in maintaining the barrier to apical acid. Our data implicate a role for an apical EGFR ligand, which may be EGF or another member of the EGF family.