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Title of Journal: J Gastroenterol

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Abbravation: Journal of Gastroenterology

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Springer Japan

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DOI

10.1006/excr.2000.5110

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1435-5922

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Hepatocyte growth factor stimulates the migration

Authors: Yuichiro Nasu Akio Ido Shirou Tanoue Shinichi Hashimoto Fumisato Sasaki Shuji Kanmura Hitoshi Setoyama Masatsugu Numata Keita Funakawa Akihiro Moriuchi Hiroshi Fujita Toshio Sakiyama Hirofumi Uto Makoto Oketani Hirohito Tsubouchi
Publish Date: 2012/06/22
Volume: 48, Issue: 2, Pages: 193-202
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Abstract

Hepatocyte growth factor HGF is essential for epithelial restitution a process in which epithelial cells rapidly migrate to cover desquamated epithelium after mucosal injury in the gastrointestinal tract In this study we aimed to elucidate the molecular mechanisms of the HGFmediated reconstitution of gastric epithelial structures by analyzing the expression and subcellular dynamics of tight junction proteinsWe treated human gastric epithelial MKN74 cells with HGF and examined the effects of HGF on cell migration and proliferation and the expression and subcellular dynamics of tight junction proteins as well we investigated the effect of HGF on paracellular permeability to macromolecules using fluorescein isothiocyanate FITCdextranHGF significantly stimulated the migration of MKN74 cells but not their proliferation in a dosedependent manner HGF did not affect the expression of tight junction proteins including claudin1 3 4 and 7 occludin and zonula occludens ZO1 However fluorescence immunostaining revealed that in the cell membrane the levels of ZO1 but not those of occludin or claudin4 were transiently decreased 1 h after HGF treatment The results were further confirmed by western blotting HGF reduced the amount of ZO1 protein in the cell membrane fraction concomitantly with an increase in cytoplasmic ZO1 Furthermore HGF reduced the interaction between ZO1 and occludin and induced the tyrosine phosphorylation of occludin whereas the phosphorylation status of ZO1 was not affected by exposure to HGF Despite a decrease in the ZO1/occludin interaction HGF did not affect paracellular permeability to macromoleculesThe authors thank Ms Yuko MorinagaNakamura for technical assistance This work was supported by GrantsinAid for Scientific Research from the Ministry of Education Culture Sports Science and Technology of Japan and by GrantsinAid from the Ministry of Health Labour and Welfare of Japan

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