Galangin inhibits hypertrophic scar formation via ALK5/Smad2/3 signaling pathway

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• 作者：Yifan Zhang ; Shengzhou Shan ; Jing Wang ; Xinyu Cheng…
• 关键词：Galangin ; Hypertrophic scar ; Fibroblasts ; ALK5 ; Smad2/3
• 刊名：Molecular and Cellular Biochemistry
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：413
• 期：1-2
• 页码：109-118
• 全文大小：3,210 KB
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• 作者单位：Yifan Zhang (1)
  Shengzhou Shan (1)
  Jing Wang (1)
  Xinyu Cheng (2)
  Bo Yi (3)
  Jia Zhou (1)
  Qingfeng Li (1)
  
  1. Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Road, Shanghai, 200011, China
  2. Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  3. Clinical College of General Hospital of Beijing Military Region, Anhui Medical University, Hefei, China
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Medical Biochemistry
  Oncology
  Cardiology
  
• 出版者：Springer Netherlands
• ISSN：1573-4919

文摘

Hypertrophic scar (HS) is characterized by excessive fibrosis associated with aberrant function of fibroblasts. Currently, no satisfactory drug has been developed to treat the disease. Here we found that a flavonoid natural product, galangin, could significantly attenuate hypertrophic scar formation in a mechanical load-induced mouse model. Both in vivo and in vitro studies demonstrated that galangin remarkably inhibited collagen production, proliferation, and activation of fibroblasts. Besides, galangin suppressed the contractile ability of hypertrophic scar fibroblasts. Further Western blot analysis revealed that galangin dose-dependently down-regulated Smad2 and Smad3 phosphorylation. Such bioactivity of galangin resulted from its selective targeting to the activin receptor-like kinase 5 (ALK5) was demonstrated by ALK5 knockdown and over-expression experiments. Taken together, this compound could simultaneously inhibit both the accumulation of collagen and abnormal activation/proliferation of fibroblasts, which were the two pivotal factors for hypertrophic scar formation, thus suggesting that galangin serves as a potential agent for treatment of HS or other fibroproliferative disorders. Keywords Galangin Hypertrophic scar Fibroblasts ALK5 Smad2/3