Keratinocyte growth factor is upregulated by the hyperplasia-inducing drug nifedipine.
Keratinocyte growth factor (KGF) is the seventh member of the fibroblast growth factor (FGF) family. It is produced by mesenchymal cells and its activity is specific for epithelial cells, controlling epithelial homeostasis and wound repair in a paracrine manner. Although KGF has been implicated in a number of hyperplastic pathologies, it has not previously been investigated in gingival hyperplasia (GH), an adverse side-effect of three pharmacologically different types of drugs, including the anti-hypertensive drug nifedipine (NIF). The mechanism by which NIF causes GH is not yet known, but we have recently shown that KGF mRNA transcripts are elevated in drug-induced GH in vivo (manuscript submitted). It is therefore possible that the action of NIF is mediated via KGF and, in the present study, using the enzyme-linked immunosorbent assay (ELISA) and the semi-quantitative reverse transcribed-polymerase chain reaction (RT-PCR), we found that NIF upregulates KGF secretion and gene transcription by gingival fibroblasts in vitro. Our results thus suggest that KGF may have an important role in the molecular pathology of GH in vivo.
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, UK.
Olsen
I
I
D000959:Antihypertensive Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D005347:Fibroblasts / Q000378:metabolism; D005881:Gingiva / Q000378:metabolism; D005885:Gingival Hyperplasia / Q000139:chemically induced; D006133:Growth Substances / Q000096:biosynthesis* / Q000737:chemistry; D006801:Humans; D009543:Nifedipine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation; D014665:Vasodilator Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D000939:Epitopes; C496453:FGF7 protein, human; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D012333:RNA, Messenger; D014665:Vasodilator Agents; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D009543:Nifedipine