Regulation of keratinocyte growth factor and scatter factor in cyclosporin-induced gingival overgrowth.
BACKGROUND
Epithelial proliferation is a histological characteristic of drug-induced gingival overgrowth. Keratinocyte growth factor (KGF) and scatter factor (SF) are fibroblast-derived growth factors with potent mitogenic and motogenic effects on epithelial cells, and, therefore, could be involved in the pathogenesis of gingival overgrowth. The aims of this study were to investigate: (i) the effects of cyclosporin on KGF and SF expression by gingival fibroblasts; and (ii) the expression levels of KGF and SF mRNA in normal and overgrown gingival tissue.


METHODS
The KGF and SF protein production was determined by enzyme-linked immunosorbent assay. Relative levels of KGF and SF mRNA expression were determined using semi-quantitative reverse transcriptase polymerase chain reaction. Expression levels in biopsies of normal and overgrown gum were also determined.


RESULTS
In overgrown fibroblasts, 500 ng/ml cyclosporin significantly inhibited KGF and SF mRNA and protein while 2000 ng/ml cyclosporin induced a stimulatory effect. In normal cells cyclosporin significantly increased both KGF and SF. KGF and SF mRNA was detected in both normal and overgrown tissues with a tendency towards increased expression levels in overgrown tissue.


CONCLUSIONS
These results suggest that KGF and SF may have an important role in cyclosporin-induced gingival overgrowth.
Hyland
P L
PL
Oral Science Research Centre, School of Dentistry, Queen's University, Belfast, Northern Ireland.
McKeown
S T W
ST
Mackenzie
I C
IC
Irwin
C R
CR
D000328:Adult; D000704:Analysis of Variance; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000096:biosynthesis*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005881:Gingiva / Q000187:drug effects / Q000378:metabolism; D019214:Gingival Overgrowth / Q000139:chemically induced* / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric
C496453:FGF7 protein, human; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D017228:Hepatocyte Growth Factor; D016572:Cyclosporine