HGF regulates tight junctions in new nontumorigenic gastric epithelial cell line.
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 degrees 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.
Hollande
F
F
Laboratoire de Biochimie des Membranes, Faculté de Pharmacie, 15 av. C. Flahault, 34060 Montpellier cedex, France. fhollande@ww3.pharma.univ-montp1.fr
Blanc
E M
EM
Bali
J P
JP
Whitehead
R H
RH
Pelegrin
A
A
Baldwin
G S
GS
Choquet
A
A
D000818:Animals; D015820:Cadherins / Q000032:analysis / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology / Q000648:ultrastructure; D017690:Cell Transplantation; D002867:Chromones / Q000494:pharmacology; D003593:Cytoplasm / Q000648:ultrastructure; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D006183:H-2 Antigens / Q000235:genetics / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D009025:Morpholines / Q000494:pharmacology; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism; D021381:Protein Transport; D019108:Tight Junctions / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D015534:Trans-Activators; D014945:Wound Healing; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D015820:Cadherins; D002867:Chromones; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D008565:Membrane Proteins; D009025:Morpholines; D010750:Phosphoproteins; C569043:Tjp1 protein, mouse; D015534:Trans-Activators; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D017228:Hepatocyte Growth Factor; D007371:Interferon-gamma