Extracellular matrix is required for MAP kinase activation and proliferation of rat glomerular epithelial cells.
This study examined the role of extracellular matrix (ECM) in the regulation of glomerular epithelial cell (GEC) proliferation. Epidermal growth factor (EGF) stimulated proliferation of GEC when the cells were adherent to collagen matrices, but not plastic substratum. Significant and prolonged EGF receptor (R) tyrosine autophosphorylation (which reflects EGF-R kinase activation) was induced by EGF only in GEC adherent to collagen. In addition, EGF stimulated the activity and tyrosine phosphorylation of p42 mitogen-activated protein (MAP) kinase (ERK2) in collagen-adherent GEC, but not in cells on plastic. An inhibitor of the p-42 MAP kinase pathway, PD98059, blocked EGF-induced MAP kinase activity and proliferation. Thus, adhesion to ECM enables EGF to induce proliferation of GEC, by facilitating activation of EGF-R and the p42 MAP kinase pathway. Signals from ECM to growth factor receptor tyrosine kinases may regulate cell turnover in the glomerulus under normal conditions and during immune glomerular injury.
Cybulsky
A V
AV
Department of Medicine, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada. cybulsky@pathology.lan.mcgill.ca
McTavish
A J
AJ
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002448:Cell Adhesion; D002455:Cell Division; D002478:Cells, Cultured; D003094:Collagen / Q000502:physiology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000201:enzymology; D066246:ErbB Receptors / Q000378:metabolism; D005109:Extracellular Matrix / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000166:cytology* / Q000201:enzymology; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D010969:Plastics; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004791:Enzyme Inhibitors; D005419:Flavonoids; D010969:Plastics; D019000:Phosphotyrosine; D004815:Epidermal Growth Factor; D003094:Collagen; D066246:ErbB Receptors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one