Specific signaling cascades involved in cell spreading during healing of micro-wounded gastric epithelial monolayers

Marie Pier Tétreault, Pierre Chailler, Jean François Beaulieu, Nathalie Rivard*, Daniel Ménard

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Mechanisms that specifically modulate cell spreading and/or cell migration following epithelial wounding are poorly understood. Using micro-wounded human gastric epithelial monolayers, we show herein that EGF and TGFα maximally increase spreading of epithelial sheets under a cell proliferation-independent mechanism. Treatment of confluent HGE-17 cells with the phosphatidylinositol 3-kinase inhibitor, LY294002, and the epidermal growth factor receptor inhibitor, PD153035, strongly reduced basal and TGFα-stimulated cell spreading. While pharmacological inhibition of pp60src-kinase activity also attenuated basal epithelial spreading, addition of the mTOR/p70S6K inhibitor rapamycin or a specific siRNA targeting ILK sequence did not affect the kinetic rates of wound closure. Epithelial wound healing was initiated by actin purse-string contraction followed by lamellae formation. Conversely, disruption of actin and tubulin stability with cytochalasin D and nocodazole, respectively, inhibited epithelial sheet spreading. Finally, antibodies directed against the α3 integrin subunit, but not against the α6 or α2 subunits, attenuated epithelial sheet spreading as well as lamellae formation. In conclusion, the current investigation establishes that EGF/TGFα and the α3β1 integrin, pp60c-src, EGFR and PI3K pathways are mainly associated with the cell spreading of the restitution process during healing of human gastric epithelial wounds.

Original languageEnglish (US)
Pages (from-to)1240-1249
Number of pages10
JournalJournal of Cellular Biochemistry
Volume105
Issue number5
DOIs
StatePublished - Dec 1 2008

Keywords

  • Cell spreading
  • EGF/TGFα
  • Gastric epithelial cells
  • Signaling pathways
  • Wound healing

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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