Epidermal and hepatocyte growth factors stimulate chemotaxis in an intestinal epithelial cell line.
The migration of intestinal cells is important in the development and maintenance of normal epithelium, in a process that may be regulated by growth factors and cytokines. Although a number of growth factor receptors are expressed by intestinal cells, little progress has been made toward assignment of functional roles for these ligand-receptor systems. This study compares several growth factors and cytokines for their chemoattraction of the mouse small intestinal epithelial cell line. Epidermal and hepatocyte growth factors stimulated a rapid 30-fold chemotaxis of cells with delayed threefold migration toward transforming growth factor-beta1. Despite stimulating proliferation, keratinocyte, fibroblast, or insulin-like growth factors did not stimulate directed migration. Chemotaxis required tyrosine kinase and phosphatidylinositol phospholipase C activities but not protein kinase C or mitogen-activated protein kinase activity. These findings suggest that the repertoire of growth factors capable of regulating directed intestinal epithelial cell migration is limited and that a divergence exists in the signal transduction pathways for directed vs. nondirected migration.
Polk
D B
DB
Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Vanderbilt University, Nashville, Tennessee 37232-2576, USA. d-brent.polk@mcmail.vanderbilt.edu
Tong
W
W
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002633:Chemotaxis / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D066246:ErbB Receptors / Q000378:metabolism; D005109:Extracellular Matrix / Q000502:physiology; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D051526:Fibroblast Growth Factor 10; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D005419:Flavonoids / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007422:Intestines / Q000166:cytology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D011799:Quinazolines; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology
D004791:Enzyme Inhibitors; C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D005419:Flavonoids; D006133:Growth Substances; D009281:Naphthalenes; D011799:Quinazolines; D016212:Transforming Growth Factor beta; D020032:Tyrphostins; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D051523:Fibroblast Growth Factor 7; C101044:RTKI cpd; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I; D019833:Genistein; D066246:ErbB Receptors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; C058819:calphostin C; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one