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 immunosuppressive drug cyclosporin A (CsA) and also certain anti-epileptic and anti-hypertensive drugs. It is characterized by a marked increase in the thickness of the epithelial layer and the accumulation of excessive amounts of connective tissue. Although the mechanism by which the drugs cause GO is not yet understood, keratinocyte growth factor (KGF), which is a potent epithelial cell mitogen, has been implicated in other hyperplastic conditions, including 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 cells using the semi-quantitative reverse transcribed-polymerase chain reaction (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 immunohistochemically 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 difference was not statistically significant.


CONCLUSIONS
This study has shown, for the first time, that the level of KGF is elevated in GO and suggests that KGF may have an important role in the enhanced epithelial proliferation associated with GO.
Das
S J
SJ
Department of Periodontology, Eastman Dental Institute for Oral Health Care Sciences, University College London, UK.
Parkar
M H
MH
Olsen
I
I
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002478:Cells, Cultured; D002648:Child; D003239:Connective Tissue Cells / Q000187:drug effects / Q000378:metabolism; D016572:Cyclosporine / Q000009:adverse effects*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D005881:Gingiva / Q000378:metabolism; D019214:Gingival Overgrowth / Q000139:chemically induced* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics
C496453:FGF7 protein, human; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D016572:Cyclosporine