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Epidermal growth factor receptor‐dependent PI3K‐activation promotes restitution of wounded human gastric epithelial monolayers
Author(s) -
Tétreault MariePier,
Chailler Pierre,
Beaulieu JeanFrancois,
Rivard Nathalie,
Ménard Daniel
Publication year - 2008
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21239
Subject(s) - microbiology and biotechnology , protein kinase b , phosphatidylinositol , pi3k/akt/mtor pathway , epidermal growth factor , kinase , wortmannin , cell migration , biology , gastric mucosa , ly294002 , growth factor , phosphorylation , signal transduction , cancer research , receptor , cell , biochemistry , stomach
Restitution is a crucial event during the healing of superficial injury of the gastric mucosa involving epithelial cell sheet movement into the damaged area. We demonstrated that growth factors promote the restitution of human gastric epithelial cells. However, the intracellular signaling pathways that transmit extracellular cues as well as regulate basal and growth factor‐stimulated gastric epithelial cell migration are still unclear. Herein, confluent human gastric epithelial cell monolayers (HGE‐17) or primary cultures of gastric epithelial cells were wounded with a razor blade and the migration response was analyzed in presence or absence of TGFα or of pharmacological inhibitors of signaling proteins. Kinase activation profile analysis and phase‐contrast microscopy were also performed in parallel. We report that ERK1/2 and Akt activities are rapidly stimulated following wounding of HGE‐17 cells. Treatment of confluent HGE‐17 cells or primary cultures of gastric epithelial cells with the phosphatidylinositol 3‐kinase inhibitor LY294002, but not the MEK1 inhibitor, PD98059, significantly inhibits basal and TGFα‐induced migration following wounding. Conversely, treatment of wounded HGE‐17 cells with phosphatidylinositol(3,4,5)‐triphosphate is sufficient to stimulate basal cell migration by 235%. In addition, pp60c‐src kinase activity and tyrosine phosphorylation of epidermal growth factor receptors (EGFR) are also rapidly enhanced after wounding and pharmacological inhibition of both these activities strongly attenuates basal and TGFα‐induced migration as well as Akt phosphorylation levels. In conclusion, the present results indicate that EGFR‐dependent PI3K activation promotes restitution of wounded human gastric epithelial monolayers. J. Cell. Physiol. 214: 545–557, 2008. © 2007 Wiley‐Liss, Inc.