HGF regulates tight junctions in new nontumorigenic gastric epithelial cell line

Author:

Hollande Frederic1,Blanc Emmanuelle M.1,Bali Jean Pierre1,Whitehead Robert H.2,Pelegrin Andre3,Baldwin Graham S.4,Choquet Armelle1

Affiliation:

1. Laboratoire de Biochimie des Membranes, Faculté de Pharmacie, 34060 Montpellier cedex, France;

2. Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Parkville, Victoria, Australia;

3. Centre Paul Lamarque, Centre Régional de lutte contre le Cancer, 34000 Montpellier, France; and

4. University Department of Surgery, Austin Campus, Melbourne, Heidelberg 3084, Victoria, Australia

Abstract

The regulation of intercellular adhesion by hepatocyte growth factor (HGF) was examined on a novel nontumorigenic gastric epithelial cell line (IMGE-5) derived from H-2Kb-tsA58 transgenic mice. IMGE-5 cells constitutively expressed cytokeratin 18 and HGF receptors. Under permissive conditions (33°C + interferon-γ), IMGE-5 cells proliferated rapidly but did not display membrane expression of adherens and tight junction proteins. Under nonpermissive conditions, their proliferation was decreased and they displayed a strong, localized membrane expression of E-cadherin/β-catenin and occludin/ZO-1. HGF treatment largely prevented the targeting of ZO-1 to the tight junction and induced a significant decrease of the transepithelial resistance measured across a confluent IMGE-5 cell monolayer. HGF rapidly increased the tyrosine phosphorylation of ZO-1 and decreased its association with occludin in a phosphatidylinositol 3-kinase (PI 3-kinase)-dependent manner. PI 3-kinase was also involved in HGF-induced migration of IMGE-5 cells. Our results demonstrate that 1) HGF prevents the appearance of ZO-1 in the membrane during epithelial cell differentiation; 2) HGF causes partial relocalization of ZO-1 to the cytoplasm and nucleus and concomitantly stimulates cell dissociation and migration; and 3) IMGE-5 cells offer a useful model for the study of gastric epithelial cell differentiation.

Publisher

American Physiological Society

Subject

Physiology (medical),Gastroenterology,Hepatology,Physiology

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