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, TGFalpha, HGF and IGFs accelerate epithelial restitution upon wounding, independently of the TGFbeta pathway (as opposed to intestinal cells). However, they differently modulate cell behavior: TGFalpha 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 TGFalpha 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.
Tétreault
Marie-Pier
MP
CIHR Group on the Functional Development and Physiopathology of the Digestive Tract, Department of Anatomy and Cell Biology, Faculty of Medicine, Université de Sherbrooke, 3001 12th Avenue N, Sherbrooke (Québec), Canada J1H 5N4.
Chailler
Pierre
P
Rivard
Nathalie
N
Ménard
Daniel
D
D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology* / Q000502:physiology; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D007365:Intercellular Junctions / Q000187:drug effects / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D062793:Occludin; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000494:pharmacology; D011554:Pseudopodia / Q000187:drug effects / Q000502:physiology; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
D015820:Cadherins; D006133:Growth Substances; D019394:Ki-67 Antigen; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D011506:Proteins; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D006918:Hydroxyurea