Keratinocyte growth factor stimulation of gelatinase (matrix metalloproteinase-9) and plasminogen activator in histiotypic epithelial cell culture.
The purpose of this investigation was to examine the role that keratinocyte growth factor (KGF) plays in the control of matrix-degrading protease activity in epithelial cells. The culture conditions had a significant effect on cellular responses to the growth factor. In histiotypic culture on porous-polycarbonate membranes, porcine periodontal ligament epithelial cells responded to KGF with increased 92-kDa gelatinase (matrix metalloproteinase [MMP]-9) activity. No such response was observed in cells maintained on plastic plates. Epidermal growth factor and platelet-derived growth factor also increased MMP-9 activity in the histiotypic cultures of epithelial cells. Addition of heparin with KGF produced a further increase in MMP-9 activity, with heparin alone having no effect. Precoating of polycarbonate membranes with matrix components showed that fibronectin and an engineered poly-RGD molecule substrate were required for KGF plus heparin to increase MMP-9 activity. Precoating plastic culture plates with the same proteins did not generate the same response. Concomitant with gelatinase activity, KGF also increased urokinase-type plasminogen activator in the epithelial cells. Thus, KGF appears to be an important regulator of protease secretion in epithelial cells.
Putnins
E E
EE
Department of Oral Biology, Faculty of Dentistry, University of British Columbia, Vancouver, Canada.
Firth
J D
JD
Uitto
V J
VJ
D000818:Animals; D002452:Cell Count / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D017364:Collagenases / Q000378:metabolism*; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004848:Epithelium; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D005353:Fibronectins / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9; D008565:Membrane Proteins / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D010960:Plasminogen Activators / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D013552:Swine
D051526:Fibroblast Growth Factor 10; D005353:Fibronectins; D006133:Growth Substances; D008565:Membrane Proteins; D010455:Peptides; D010982:Platelet-Derived Growth Factor; C065723:poly (arginyl-glycyl-aspartic acid); D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D006493:Heparin; D010960:Plasminogen Activators; D017364:Collagenases; D020780:Matrix Metalloproteinase 9