title: Cyclosporine A induces connective tissue growth factor expression in human gingival fibroblasts: suppression by epigallocatechin-3-gallate.
abstract: OBJECTIVE
  Transforming growth factor-β (TGF-β) plays an important role in the pathogenesis of cyclosporine A (CsA)-induced gingival overgrowth (GO). Connective tissue growth factor (CTGF/CCN2) acts as a cofactor with TGF-β to induce the maximal profibrotic effects of TGF-β. We investigated the effects of CsA on CCN2 expression in human gingival fibroblasts (HGFs) and the potential chemopreventive agent for CsA-induced GO.
  
  
  METHODS
  Western blot analyses were used to examine the signaling pathways of CsA-induced CCN2 expression in HGFs and whether epigallocatechin-3-gallate (EGCG), curcumin, or lovastatin can inhibit CsA-induced CCN2 expression.
  
  
  RESULTS
  CsA significantly stimulated CCN2 synthesis in HGFs. This effect can be inhibited by c-Jun NH(2)-terminal kinase (JNK) and Smad3 inhibitors but not by TGF-β neutralizing antibody and TGF-β type I receptor inhibitor. Furthermore, EGCG completely blocked CsA-induced CCN2 expression.
  
  
  CONCLUSIONS
  CsA-induced CCN2 protein expression is mediated through JNK and Smad signaling. CsA may contribute to the pathogenesis of GO through upregulation of CCN2 expression in HGFs. EGCG could be an adjuvant for the prevention of CsA-induced GO.
authors.affiliation: Department of Dentistry, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan.
authors.forename: King-Jean
authors.initials: KJ
authors.lastname: Wu
authors.affiliation: Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Guay-Fen
authors.initials: GF
authors.lastname: Huang
authors.affiliation: Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Hao-Hueng
authors.initials: HH
authors.lastname: Chang
authors.affiliation: Department of Dentistry, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan. Electronic address: q95422002@ntu.edu.tw.
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Deng
mesh_terms: D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D016572:Cyclosporine / Q000009:adverse effects*; D005347:Fibroblasts / Q000187:drug effects*; D005881:Gingiva / Q000166:cytology; D019214:Gingival Overgrowth / Q000139:chemically induced*; D006801:Humans; D061251:Primary Cell Culture; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: C526317:CCN2 protein, human; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D016572:Cyclosporine; D002392:Catechin; C045651:epigallocatechin gallate
keywords: connective tissue growth factor/CCN2; cyclosporine; epigallocatechin-3-gallate; fibroblast; gingival overgrowth