title: Role of transforming growth factor-beta1 in cyclosporine-induced epithelial-to-mesenchymal transition in gingival epithelium.
abstract: BACKGROUND
  It has been proposed that cyclosporin A (CsA) may induce epithelial-to-mesenchymal transition (EMT) in gingiva. The aims of the present study are to confirm the notion that EMT occurs in human gingival epithelial (hGE) cells after CsA treatment and to investigate the role of transforming growth factor beta1 (TGF-β1) on this CsA-induced EMT.
  
  
  METHODS
  The effects of CsA, with and without TGF-β1 inhibitor, on the morphologic changes of primary culture of hGE cells were examined in vitro. The changes of protein and messenger RNA (mRNA) expressions of two EMT markers (E-cadherin and alpha-smooth muscle actin) in the hGE cells after CsA treatment with and without TGF-β1 inhibitor were evaluated with immunocytochemistry and real-time polymerase chain reaction.
  
  
  RESULTS
  The epithelial cells became spindle-like, elongated, and disassociated from neighboring cells and lost their original cobblestone monolayer pattern when CsA was added. However, the epithelial cells stayed in their original cobblestone morphology with treatment of TGF-β1 inhibitor on top of the CsA treatment. When CsA was given, the protein and mRNA expressions of E-cadherin and α-SMA were significantly altered, and these alterations were significantly reversed with pretreatment of TGF-β1 inhibitor.
  
  
  CONCLUSIONS
  CsA could induce Type 2 EMT in gingiva by changing the morphology of epithelial cells and altering the EMT markers/effectors. The CsA-induced gingival EMT is dependent or at least partially dependent on TGF-β1.
authors.affiliation: Department of Periodontology, School of Dentistry, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan, ROC.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Fu
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Chin
authors.forename: Earl
authors.initials: E
authors.lastname: Fu
authors.forename: Hsien-Chung
authors.initials: HC
authors.lastname: Chiu
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Wang
authors.forename: Cheng-Yang
authors.initials: CY
authors.lastname: Chiang
authors.forename: Hsiao-Pei
authors.initials: HP
authors.lastname: Tu
mesh_terms: D000199:Actins / Q000187:drug effects; D000328:Adult; D015820:Cadherins / Q000187:drug effects; D018929:Cell Culture Techniques; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D016572:Cyclosporine / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D005881:Gingiva / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D051899:Smad2 Protein / Q000187:drug effects; D051900:Smad3 Protein / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D015820:Cadherins; D003470:Culture Media; D007166:Immunosuppressive Agents; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D016572:Cyclosporine
keywords: Alpha-smooth muscle actin; cadherins; cyclosporine; epithelial-mesenchymal transition; gingiva; smad2 protein; smad3 protein; transforming growth factor beta1