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Am J Physiol Gastrointest Liver Physiol 280: G910-G921, 2001;
0193-1857/01 $5.00
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Vol. 280, Issue 5, G910-G921, May 2001

HGF regulates tight junctions in new nontumorigenic gastric epithelial cell line

Frederic Hollande1, Emmanuelle M. Blanc1, Jean Pierre Bali1, Robert H. Whitehead2, Andre Pelegrin3, Graham S. Baldwin4, and Armelle Choquet1

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

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-gamma ), 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/beta -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.

hepatocyte growth factor; ZO-1; occludin; gastric epithelial cell line; ImmortoMouse


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