HGF regulates tight junctions in new nontumorigenic gastric epithelial cell line

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 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.

Development and Characterization of Conditionally Immortalized Gastric Epithelial Cell Lines from Transgenic Rats Harboring Temperature-Sensitive Simian Virus 40 Large T-antigen Gene.

“…Further studies are needed to find the experimental conditions under which the cells produce mucin. Recently, Hollande et al (2001) reported establishing a gastric epithelial cell line, IMGE-5, which displays membrane expression of adhesion and tight junction proteins from the tsSV40 large T-antigen TG mice. However, the cells did not express specific markers for pit, parietal, or zymogenic cells.…”

“…Thus far, various cell lines with specific functions from different organs have been established by using TG mice, e.g., hepatocytes (Yanai et al, 1991), colonic epithelial cells (Tabuchi et al, 2000), testicular Leydig and Sertoli cells . Furthermore, we and others have succeeded in establishing pit (gastric surface mucous) cell lines, GSM06 and GSM10 (Sugiyama et al, 1993;Tabuchi, 2001), and a gastric epithelial cell line, IMGE-5, from the TG mice (Hollande et al, 2001). More recently, TG rat harboring the tsSV40 large Tantigen gene was also developed as a source of conditionally immortalized cell lines (Takahashi et al, 1999).…”

Epidermal Growth Factor Receptor Activation Differentially Regulates Claudin Expression and Enhances Transepithelial Resistance in Madin-Darby Canine Kidney Cells

“…HGF is known to decrease TER in many cell lines (51,52); and unlike EGF, HGF induces epithelial-mesenchymal transitions in MDCK II cells grown on plastic (53). Quiescent and polarized MDCK cells were treated with 20 ng/ml HGF, a concentration known to induce cell scattering in MDCK cells (54); and changes in claudin expression were determined.…”

Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells

“…[26][27][28] The dynamic nature of tight junctions is well demonstrated by the ability of cytokines and growth factors to modulate tight junction protein expression, regulate junction assembly and change epithelial permeability. [29][30][31][32][33] It has been established for many years that the cytokine profile of CD is T-helper type 1 and shows increased expression of the cytokines, TNFa and IFNg. 34,35 The situation in ulcerative colitis (UC) is less clear.…”