title: Asiaticoside hinders the invasive growth of keloid fibroblasts through inhibition of the GDF-9/MAPK/Smad pathway.
abstract: Higher expression of growth differentiation factor-9 (GDF-9) in keloids compared with hypertrophic scars and normal skin tissues has been reported recently. The present study was performed to investigate the role of GDF-9 in keloid pathogenesis, and to elucidate its implication for asiaticoside in the keloid management. The data showed that GDF-9 could enhance the proliferation, migration, and invasion of keloid fibroblasts (KFs), while it only slightly elevated collagen expression, indicating that the effect of GDF-9 was opposite to that of TGF-β1. The bioactivity difference between GDF-9 and TGF-β1 could be explained by the different phosphorylated sites on the downstream Smad2/3. Moreover, asiaticoside could inhibit GDF-9-induced activation of MAPKs and Smad pathway in KFs. In conclusion, GDF-9 enhanced the invasive growth of KFs, which was achieved by phosphorylation of Smad 2/3 at the linker region through activation of MAPKs pathway. Asiaticoside hindered the invasive growth of KFs by inhibiting the GDF-9/MAPK/Smad pathway.
authors.affiliation: Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wu
authors.affiliation: Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
authors.forename: Difei
authors.initials: D
authors.lastname: Bian
authors.affiliation: Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
authors.forename: Yannong
authors.initials: Y
authors.lastname: Dou
authors.affiliation: Center for New Drug Research & Development, College of Life Science, Nanjing Normal University, Nanjing, 210024, People's Republic of China.
authors.forename: Zhunan
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Tan
authors.affiliation: Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Dai
mesh_terms: D000293:Adolescent; D000328:Adult; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D055429:Growth Differentiation Factor 9 / Q000378:metabolism*; D006801:Humans; D007627:Keloid / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: C525897:GDF9 protein, human; D055429:Growth Differentiation Factor 9; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D014315:Triterpenes; C004446:asiaticoside
keywords: GDF-9; TGF-β1; asiaticoside; keloid