title: Elevated Snail expression in human gingival fibroblasts by cyclosporine A as the possible pathogenesis for gingival overgrowth.
abstract: OBJECTIVE
  Cyclosporine A (CsA) is used as an immunosuppressive agent, and its prominent side effect is the induction of gingival overgrowth. Snail is a master regulator of epithelial-mesenchymal transition (EMT). EMT under pathological processes could lead to fibrotic changes. The purpose of this study was to investigate the role of Snail in the pathogenesis of CsA-induced gingival overgrowth.
  
  
  METHODS
  The effect of CsA on normal human gingival fibroblasts (HGFs) was used to elucidate whether Snail expression could be induced by CsA by using quantitative real-time reverse transcription-polymerase chain reaction and western blot. The cell proliferation rate in CsA-treated HGFs with Snail lentiviral-mediated short hairpin RNA interference (shRNAi) knockdown was evaluated by tetrazolium bromide reduction assay.
  
  
  RESULTS
  CsA increased the Snail transcript and Snail protein expression in HGFs in a dose-dependent manner (p < 0.05). In addition, downregulation of Snail by lentiviral infection significantly reduced CsA-stimulated cell proliferation in HGFs (p < 0.05).
  
  
  CONCLUSIONS
  CsA stimulated Snail expression and cell proliferation in HGFs, while silencing Snail could effectively reverse these phenomena. These results may provide new avenues for the design of novel antifibrotic therapies for CsA-induced gingival overgrowth through targeting Snail.
authors.affiliation: Division of Periodontics, Department of Dentistry, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Yi-Hung
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Cheng-Chia
authors.initials: CC
authors.lastname: Yu
authors.affiliation: School of Public Health, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Shiuan-Shinn
authors.initials: SS
authors.lastname: Lee
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan. Electronic address: cyc@csmu.edu.tw.
authors.forename: Yu-Chao
authors.initials: YC
authors.lastname: Chang
mesh_terms: D002478:Cells, Cultured; D016572:Cyclosporine / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects*; D005881:Gingiva / Q000166:cytology*; D019214:Gingival Overgrowth / Q000139:chemically induced*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015854:Up-Regulation / Q000187:drug effects; D016335:Zinc Fingers / Q000187:drug effects*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine
keywords: Snail; cyclosporine A; gingival overgrowth; human gingival fibroblasts