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CLATHRIN-COATED PIT ENDOCYTOSIS MEDIATES HELICOBACTER PYLORI-INDUCED CYTOSOLIC TRANSLOCATION OF TIGHT JUNCTIONAL CLAUDIN-4 IN HUMAN GASTRIC EPITHELIAL CELLS

TK Lapointe¹, PM O'Connor¹, TD Feener¹, D Menard², AG Buret¹
¹Biological Sciences and Inflammation Research Network, University of Calgary, Calgary, Alberta; ²University of Sherbrooke, Sherbrooke, Quebec

H. pylori (Hp) infects half of the human population and can cause gastritis, gastroduodenal ulcers, and gastric adenocarcinoma. The ability of Hp to disrupt epithelial barrier function may influence the clinical outcome of infection. However, the direct effects of Hp on the gastric epithelium are incompletely understood. Redistribution of tight junctional (TJ) proteins within the cell is an important modulator of gastric epithelial function. Internalization of TJ proteins promotes the rapid loss of intercellular adhesion and a subsequent increase in epithelial permeability.
AIM: The aim of this study was to characterize the mechanisms by which Hp disrupts epithelial barrier structure and function in vitro using the human gastric epithelial (HGE-20) cell line.
RESULTS: Hp strain SS1 significantly increased transepithelial fluxes of FITC-dextran (3000MW). Immunocytochemistry and Western blotting revealed that Hp SS1 induced the reorganization of TJ protein claudin-4 from the membrane to the cytosoplasmic compartment in HGE-20 monolayers. Furthermore, claudin-4 is translocated to areas of the cell occupied by the golgi apparatus. Inhibition of clathrin-coated pit endocytosis by cytosolic acidification prior to infection prevented these effects.
CONCLUSION: The data indicate that, in the absence of any immune cell, Hp directly alters epithelial barrier structure and function in this model. The mechanisms involve, at least in part, the tight junction to cytosol translocation of claudin-4 via clathrin-coated pit-mediated endocytosis.

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