Asiaticoside hinders the invasive growth of keloid fibroblasts through inhibition of the GDF‐9/MAPK/Smad pathway

• Published in: Journal of biochemical and molecular toxicology Vol. 31; no. 8
• Main Authors: Wu, Xin, Bian, Difei, Dou, Yannong, Gong, Zhunan, Tan, Qian, Xia, Yufeng, Dai, Yue
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.08.2017
• Subjects: Activation; Adolescent; Adult; asiaticoside; Biocompatibility; Biological activity; Cell Movement - drug effects; Cell Proliferation - drug effects; Collagen; Differentiation; Eutrophication; Female; Fibroblasts; Fibroblasts - metabolism; Fibroblasts - pathology; GDF‐9; Growth Differentiation Factor 9 - metabolism; Humans; keloid; Keloid - metabolism; Keloid - pathology; MAP kinase; MAP Kinase Signaling System - drug effects; Migration; Pathogenesis; Phosphorylation; Phosphorylation - drug effects; Scars; Skin; Smad protein; Smad2 protein; Smad2 Protein - metabolism; Smad3 Protein - metabolism; TGF‐β1; Tissues; Transforming Growth Factor beta1 - metabolism; Triterpenes - pharmacology; keloid; TGF-β1; asiaticoside; GDF-9
• ISSN: 1095-6670; 1099-0461
• DOI: 10.1002/jbt.21922

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.