title: Kaempferol inhibits fibroblast collagen synthesis, proliferation and activation in hypertrophic scar via targeting TGF-β receptor type I.
abstract: Hypertrophic scar (HPS) formation is a debilitating condition that results in pain, esthetic symptom and loss of tissue function. So far, no satisfactory therapeutic approach has been available for HPS treatment. In this study, we discovered that a natural small molecule, kaempferol, could significantly inhibit HPS formation in a mechanical load-induced mouse model. Our results also demonstrated that kaempferol remarkably attenuated collagen synthesis, proliferation and activation of fibroblasts in vitro and in vivo. Western blot analysis further revealed that kaempferol significantly down-regulated Smad2 and Smad3 phosphorylation in a dose-dependent manner. At last, we found that such bioactivity of kaempferol which resulted from the inhibition of TGF-β1/Smads signaling was induced by the selective binding of kaempferol to TGF-β receptor type I (TGFβRI). These findings suggest that kaempferol could be developed into a promising agent for the treatment of HPS or other fibroproliferative disorders.
authors: Department of Pediatric Surgery, Zhejiang Minzheng Rehabilitation Center, Zhejiang, China. Electronic address: dr.hongweili@hotmail.com.
authors: Hongwei
authors: H
authors: Li
authors: Zhejiang Chinese Medical University, Zhejiang, China. Electronic address: drliuyang82@126.com.
authors: Liu
authors: L
authors: Yang
authors: Department of General Surgery, The Children's Hospital, Zhejiang University School of Medicine, Zhejiang, China. Electronic address: pedsurgao@gmail.com.
authors: Yuebing
authors: Y
authors: Zhang
authors: Department of General Surgery, The Children's Hospital, Zhejiang University School of Medicine, Zhejiang, China. Electronic address: ebwk@zju.edu.cn.
authors: Zhigang
authors: Z
authors: Gao
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017439:Cicatrix, Hypertrophic / Q000378:metabolism* / Q000473:pathology*; D003094:Collagen / Q000096:biosynthesis*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D044949:Kaempferols / Q000494:pharmacology*; D008297:Male; D008807:Mice, Inbred BALB C; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: D044949:Kaempferols; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; C006552:kaempferol; D003094:Collagen
keywords: Fibroblasts; Hypertrophic scar; Kaempferol; TGF-β1/Smads; TGFβRI