title: Effect of nifedipine on the expression of keratinocyte growth factor and its receptor in cocultured/monocultured fibroblasts and keratinocytes.
abstract: OBJECTIVE
  Keratinocyte growth factor (KGF) and its receptor (KGFR) are involved in hyperplastic diseases. This study explored the effect of intercellular communication on KGF and KGFR in cocultured/monocultured gingival fibroblasts and keratinocytes following treatment with nifedipine.
  
  
  METHODS
  Human gingival fibroblasts and keratinocytes were monocultured and cocultured, respectively. MTT was used to investigate the effects of nifedipine on the proliferation of gingival fibroblasts and keratinocytes. Monoculture and coculture systems were treated with different concentrations (0, 0.2 or 20 μg/mL) of nifedipine, and the expression of KGF and KGFR mRNAs was examined by RT-PCR, whilst the secretion of KGF and the expression of KGFR on the membrane were analyzed using ELISA and flow cytometry, respectively.
  
  
  RESULTS
  Nifedipine (0, 0.2 and 20 μg/mL) had no influence on cell proliferation within 3 d. KGF and KGFR mRNAs were up-regulated, but only in the cocultures. In coculture, the secretion of KGF was significantly increased by nifedipine, while it was only significantly up-regulated by 20 μg/mL of nifedipine in monoculture. Moreover, the level of KGFR protein in the membrane was significantly increased by 20 μg/mL of nifedipine in monocultures, while it was significantly down-regulated by 20 μg/mL of nifedipine in cocultures.
  
  
  CONCLUSIONS
  The expression of KGF and KGFR are influenced by the interplay of gingival keratinocytes and fibroblasts. Epithelial keratinocytes and mesenchymal fibroblasts may interplay to dynamically regulate gene expression, which may have an effect on the gingival condition following treatment with nifedipine.
authors.affiliation: Institute of Stomatology, Nanjing Medical University, Nanjing, China; Department of Periodontology, College of Stomatology, Nanjing Medical University, Nanjing, China.
authors.forename: C-P
authors.initials: CP
authors.lastname: Di
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: C
authors.initials: C
authors.lastname: Ding
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.forename: Y
authors.initials: Y
authors.lastname: Fan
mesh_terms: D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects; D018929:Cell Culture Techniques; D002462:Cell Membrane / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D004396:Coloring Agents; D051523:Fibroblast Growth Factor 7 / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000187:drug effects*; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D002121:Calcium Channel Blockers; D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D051523:Fibroblast Growth Factor 7; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor; C022616:thiazolyl blue; D009543:Nifedipine
keywords: coculture; keratinocyte growth factor; keratinocyte growth factor receptor; nifedipine-induced gingival overgrowth