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Title: Differential growth factor induction and modulation of human gastric epithelial regeneration

While several autocrine/paracrine growth factors (GFs) can all stimulate epithelial regeneration in experimentally wounded primary gastric cultures, clinical relevance for their non-redundant cooperative actions in human gastric ulcer healing is suggested by the sequential pattern of GF gene induction in vivo. Using new HGE cell lines able to form a coherent monolayer with tight junctions as well as using primary human gastric epithelial cultures, we show that EGF, TGF{alpha}, HGF and IGFs accelerate epithelial restitution upon wounding, independently of the TGF{beta} pathway (as opposed to intestinal cells). However, they differently modulate cell behavior: TGF{alpha} exerts strong effects (even more than EGF) on cytoplasmic spreading and non-oriented protruding activity of bordering cells whereas HGF preferentially coordinates single lamella formation, cell elongation and migration into the wound. IGF-I and IGF-II rather induce the alignment of bordering cells and maintain a compact monolayer front. The number of mitotic cells maximally increases with EGF, followed by TGF{alpha} and IGF-I,-II. The current study demonstrates that GFs differentially regulate the regeneration of human gastric epithelial cells through specific modulation of cell shape adaptation, migration and proliferation, further stressing that a coordination of GF activities would be necessary for the normal progression of post-wounding epithelial repair.
Authors:
 [1] ;  [1] ;  [1] ;  [2]
  1. CIHR Group on the Functional Development and Physiopathology of the Digestive Tract, Department of Anatomy and Cell Biology, Faculty of Medicine, Universite de Sherbrooke, 3001 12th Avenue N, Sherbrooke (Quebec), J1H 5N4 (Canada)
  2. CIHR Group on the Functional Development and Physiopathology of the Digestive Tract, Department of Anatomy and Cell Biology, Faculty of Medicine, Universite de Sherbrooke, 3001 12th Avenue N, Sherbrooke (Quebec), J1H 5N4 (Canada). E-mail: Daniel.Menard@USherbrooke.ca
Publication Date:
OSTI Identifier:
20717609
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 306; Journal Issue: 1; Other Information: DOI: 10.1016/j.yexcr.2005.02.019; PII: S0014-4827(05)00085-6; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BIOLOGICAL REPAIR; CELL PROLIFERATION; ELECTROPHORESIS; ELONGATION; GELS; GROWTH FACTORS; HEALING; IN VIVO; INSULIN; RATS; SCANNING ELECTRON MICROSCOPY; SODIUM; STOMACH; SULFATES; ULCERS; WOUNDS