title: Effect of Botulinum Toxin Type A on TGF-β/Smad Pathway Signaling: Implications for Silicone-Induced Capsule Formation.
abstract: BACKGROUND
  One of the most serious complications of breast surgery using implants is capsular contracture. Several preventive treatments have been introduced; however, the mechanism of capsule formation has not been resolved completely. The authors previously identified negative effects of botulinum toxin type A on capsule formation, expression of transforming growth factor (TGF)-β1, and differentiation of fibroblasts into myofibroblasts. Thus, the authors investigated how to prevent capsule formation by using botulinum toxin type A, particularly by means of TGF-β1 signaling, in human fibroblasts.
  
  
  METHODS
  In vitro, cultured human fibroblasts were treated with TGF-β1 and/or botulinum toxin type A. Expression of collagen, matrix metalloproteinase, and Smad was examined by Western blotting. The activation of matrix metalloproteinase was observed by gelatin zymography. In vivo, the effect of botulinum toxin type A on the phosphorylation of Smad2 in silicone-induced capsule formation was evaluated by immunocytochemistry.
  
  
  RESULTS
  In vitro, the phosphorylation of Smad2 was inhibited by botulinum toxin type A treatment. The expression levels of collagen types 1 and 3 were inhibited by botulinum toxin type A treatment, whereas those of matrix metalloproteinase-2 and matrix metalloproteinase-9 were enhanced. Gelatin zymography experiments confirmed enhanced matrix metalloproteinase-2 activity in collagen degradation. In vivo, botulinum toxin type A treatment reduced capsule thickness and Smad2 phosphorylation in silicone-induced capsules.
  
  
  CONCLUSIONS
  This study suggests that botulinum toxin type A plays an important role in the inhibition of capsule formation through the TGF-β/Smad signaling pathway.
  
  
  METHODS
  Therapeutic, V.
authors.affiliation: Daejeon, Republic of Korea.|From the Departments of Plastic Surgery, Anatomy, General Surgery, and Dermatology and the Brain Research Institute, Collage of Medicine, Chungnam National University.
authors.forename: Sena
authors.initials: S
authors.lastname: Kim
authors.affiliation: Daejeon, Republic of Korea.|From the Departments of Plastic Surgery, Anatomy, General Surgery, and Dermatology and the Brain Research Institute, Collage of Medicine, Chungnam National University.
authors.forename: Moonsang
authors.initials: M
authors.lastname: Ahn
authors.affiliation: Daejeon, Republic of Korea.|From the Departments of Plastic Surgery, Anatomy, General Surgery, and Dermatology and the Brain Research Institute, Collage of Medicine, Chungnam National University.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Piao
authors.affiliation: Daejeon, Republic of Korea.|From the Departments of Plastic Surgery, Anatomy, General Surgery, and Dermatology and the Brain Research Institute, Collage of Medicine, Chungnam National University.
authors.forename: Yooseok
authors.initials: Y
authors.lastname: Ha
authors.affiliation: Daejeon, Republic of Korea.|From the Departments of Plastic Surgery, Anatomy, General Surgery, and Dermatology and the Brain Research Institute, Collage of Medicine, Chungnam National University.
authors.forename: Dae-Kyoung
authors.initials: DK
authors.lastname: Choi
authors.affiliation: Daejeon, Republic of Korea.|From the Departments of Plastic Surgery, Anatomy, General Surgery, and Dermatology and the Brain Research Institute, Collage of Medicine, Chungnam National University.
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Yi
authors.affiliation: Daejeon, Republic of Korea.|From the Departments of Plastic Surgery, Anatomy, General Surgery, and Dermatology and the Brain Research Institute, Collage of Medicine, Chungnam National University.
authors.forename: Nara
authors.initials: N
authors.lastname: Shin
authors.affiliation: Daejeon, Republic of Korea.|From the Departments of Plastic Surgery, Anatomy, General Surgery, and Dermatology and the Brain Research Institute, Collage of Medicine, Chungnam National University.
authors.forename: Dong Woon
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Daejeon, Republic of Korea.|From the Departments of Plastic Surgery, Anatomy, General Surgery, and Dermatology and the Brain Research Institute, Collage of Medicine, Chungnam National University.
authors.forename: Sang-Ha
authors.initials: SH
authors.lastname: Oh
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D019274:Botulinum Toxins, Type A / Q000494:pharmacology* / Q000627:therapeutic use; D018427:Breast Implants; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D057910:Implant Capsular Contracture / Q000517:prevention & control; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009465:Neuromuscular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D020034:Silicone Gels; D051899:Smad2 Protein / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D024061:Collagen Type III; D009465:Neuromuscular Agents; C497782:SMAD2 protein, human; D020034:Silicone Gels; D051899:Smad2 Protein; D053773:Transforming Growth Factor beta1; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D019274:Botulinum Toxins, Type A