title: Galangin inhibits hypertrophic scar formation via ALK5/Smad2/3 signaling pathway.
abstract: 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.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Road, Shanghai, 200011, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Road, Shanghai, 200011, China.
authors.forename: Shengzhou
authors.initials: S
authors.lastname: Shan
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Road, Shanghai, 200011, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Clinical College of General Hospital of Beijing Military Region, Anhui Medical University, Hefei, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yi
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Road, Shanghai, 200011, China. joyjb@163.com.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Road, Shanghai, 200011, China. dr.liqingfeng@yahoo.com.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Li
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D017439:Cicatrix, Hypertrophic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000235:genetics* / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D005419:Flavonoids; D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; C037032:galangin; D003094:Collagen; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; C000625842:Tgfbr1 protein, mouse
keywords: ALK5; Fibroblasts; Galangin; Hypertrophic scar; Smad2/3