title: Laminins and TGF-beta maintain cell polarity and functionality of human gastric glandular epithelium.
abstract: The human gastric glandular epithelium produces a gastric lipase enzyme (HGL) that plays an important role in digestion of dietary triglycerides. To assess the involvement of extracellular matrix components and transforming growth factor-beta1 (TGF-beta1) in the regulation of this enzymic function, normal gastric epithelial cells were cultured on collagen type I, Matrigel, and laminins (LN)-1 and -2 with or without TGF-beta1. Epithelial morphology and HGL expression were evaluated using microscopy techniques, enzymic assays, Western blot, Northern hybridization, and RT-PCR. A correlation was observed between the cell polarity status and the level of HGL expression. TGF-beta1 alone or individual matrix components stimulated cell spreading and caused a downfall of HGL activity and mRNA. By contrast, Matrigel preserved the morphological features of differentiated epithelial cells and maintained HGL expression. The combination of LNs with TGF-beta1 (two constituents of Matrigel) exerted similar beneficial effects on epithelial cell polarity and evoked a 10-fold increase of HGL levels that was blunted by a neutralizing antibody against the alpha(2)-integrin subunit and by mitogen-activated protein kinase (MAPK) inhibitors PD-98059 (p42/p44) or SB-203580 (p38). This investigation demonstrates for the first time that a powerful synergism between a growth factor and basement membrane LNs positively influences cell polarity and functionality of the human gastric glandular epithelium through an activation of the alpha(2)beta(1)-integrin and effectors of two MAPK pathways.
authors.affiliation: Canadian Institute of Health Research Group on the Functional Development and Physiopathology of the Digestive Tract, Department of Anatomy and Cell Biology, Université de Sherbrooke, 3001 12th Avenue N, Sherbrooke, Quebec, Canada J1H 5N4.
authors.forename: Jean-René
authors.initials: JR
authors.lastname: Basque
authors.forename: Pierre
authors.initials: P
authors.lastname: Chailler
authors.forename: Daniel
authors.initials: D
authors.lastname: Ménard
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001672:Biocompatible Materials / Q000494:pharmacology; D002299:Cardia / Q000166:cytology; D016764:Cell Polarity / Q000187:drug effects*; D002478:Cells, Cultured; D019872:Chief Cells, Gastric / Q000201:enzymology* / Q000648:ultrastructure; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D004357:Drug Synergism; D004847:Epithelial Cells / Q000201:enzymology / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000494:pharmacology; D005333:Fetus / Q000166:cytology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D039421:Integrin alpha2; D007797:Laminin / Q000494:pharmacology*; D008049:Lipase / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008854:Microscopy, Electron; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010434:Pepsin A / Q000378:metabolism; D011509:Proteoglycans / Q000494:pharmacology; D011706:Pyloric Antrum / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D015703:Antigens, CD; D001672:Biocompatible Materials; D004338:Drug Combinations; D016326:Extracellular Matrix Proteins; D039421:Integrin alpha2; D007797:Laminin; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; C121346:laminin 1; C059485:matrigel; D003094:Collagen; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D008049:Lipase; D010434:Pepsin A