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

摘要

Abstract Higher expression of growth differentiation factor9 (GDF9) in keloids compared with hypertrophic scars and normal skin tissues has been reported recently. The present study was performed to investigate the role of GDF9 in keloid pathogenesis, and to elucidate its implication for asiaticoside in the keloid management. The data showed that GDF9 could enhance the proliferation, migration, and invasion of keloid fibroblasts (KFs), while it only slightly elevated collagen expression, indicating that the effect of GDF9 was opposite to that of TGF? The bioactivity difference between GDF9 and TGF?could be explained by the different phosphorylated sites on the downstream Smad2/3. Moreover, asiaticoside could inhibit GDF9induced activation of MAPKs and Smad pathway in KFs. In conclusion, GDF9 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 GDF9/MAPK/Smad pathway.