Up-regulation of keratinocyte growth factor and receptor: a possible mechanism of action of phenytoin in wound healing.
A number of studies suggest that keratinocyte growth factor (KGF) plays a major part in reepithelialisation after injury, via binding to the specific KGF receptor (KGFR). Several pharmacological agents, including the anti-epileptic drug phenytoin (PHT), have been widely used clinically to promote wound healing. Although the mechanism of action of PHT in this process is still not well understood, it is possible that the activity of PHT in wound healing is mediated via KGF and the KGFR. In the present study, using the enzyme-linked immunosorbant assay and flow cytometry we have shown that PHT increases KGF secretion and KGFR expression by more than 150% in gingival fibroblasts and epithelial cells, respectively. Moreover, semi-quantitative reverse transcriptase-polymerase chain reaction analysis showed that PHT also markedly increased both KGF and KGFR gene transcription by these cells. Our findings thus suggest that the wound healing activity of PHT in vivo may be mediated, at least partly, via KGF and its receptor.
Das
S J
SJ
Department of Periodontology, Eastman Dental Institute for Oral Health Care Sciences, University College London, University of London, 256 Gray's Inn Road, London, WC1X 8LD, United Kingdom.
Olsen
I
I
D000328:Adult; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000096:biosynthesis / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D005881:Gingiva / Q000166:cytology*; D006801:Humans; D008297:Male; D010672:Phenytoin / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D015533:Transcriptional Activation; D015854:Up-Regulation; D014945:Wound Healing
C496453:FGF7 protein, human; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor; D051523:Fibroblast Growth Factor 7; D010672:Phenytoin; D005346:Fibroblast Growth Factors; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor