Effect of Botulinum Toxin Type A on TGF-beta/Smad pathway signaling: Implications for Silicone-induced Capsule Formation.

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. We previously identified negative effects of botulinum toxin type A (BTX-A) on capsule formation, expression of TGF-[beta]1 and differentiation of fibroblasts into myofibroblasts. Thus, we investigated how to prevent capsule formation by BTX-A, particularly via TGF-[beta]1 signaling, in human fibroblasts. Methods: In vitro, cultured human fibroblasts were treated with TGF-[beta]1 and/or BTX-A. The expression of collagen, matrix metalloproteinase (MMP), and Smad were examined by Western blotting. The activation of MMP was observed by gelatin zymography. In vivo, the effect of BTX-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 BTX-A treatment. The expression levels of collagen types 1 and 3 were inhibited by BTX-A treatment, while those of MMP2 and MMP9 were enhanced. Gelatin zymography experiments confirmed enhanced MMP2 activity in collagen degradation. In vivo, BTX-A treatment reduced capsule thickness and Smad2 phosphorylation in silicone-induced capsules. Conclusion: Our study suggested that BTX-A plays an important role in the inhibition of capsule formation through the TGF-[beta]/Smad signaling pathway. (C)2016American Society of Plastic Surgeons

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