Upregulation of keratinocyte growth factor in cyclosporin A-induced gingival overgrowth

Background: Drug-induced gingival overgrowth (GO) is a frequent and adverse side-effect associated principally with the administration of the immunosu ppressive drug cyclosporin A (CsA) and also certain anti-epileptic and anti -hypertensive drugs. It is characterized by a marked increase in the thickn ess of the epithelial layer and the accumulation of excessive amounts of co nnective tissue. Although the mechanism by which the drugs cause GO is not yet understood, keratinocyte growth factor (KGF), which is a potent epithel ial cell mitogen, has been implicated in other hyperplastic conditions, inc luding mammary and prostatic hyperplasia, and could also be involved in the molecular pathology of GO. Methods: Immunohistochemistry was used to examine the expression of KGF in normal gingiva (NG) and GO tissue sections. The relative level of KGF mRNA in GO tissue and cells was compared with that of NG tissue and fibroblast c ells using the semi-quantitative reverse transcribed-polymerase chain react ion (RT-PCR) and DNA sequencing was carried out to confirm the identity of the PCR product. Results: KGF antigen and mRNA were readily detected in the GO tissue immuno histochemically and by RT-PCR, respectively, but were not expressed in the NG tissue. Moreover, KGF transcripts were found to be approximately 2 times higher in the GO than in the NG fibroblasts in vitro, although the differe nce was not statistically significant. Conclusions: This study has shown, for the first time, that the level of KG F is elevated in GO and suggests that KGF may have an important role in the enhanced epithelial proliferation associated with GO.