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. CONCLUSION: These results suggest that KGF and SF may have an important role in cyclosporin-induced gingival overgrowth.