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.

Time Series Integrative Analysis of RNA Sequencing and MicroRNA Expression Data Reveals Key Biologic Wound Healing Pathways in Keloid-Prone Individuals

“…Of note, NOTCH signaling, mitogenactivated protein kinase signaling, and Toll-like receptor pathways were found to be altered in keloid-prone individuals after wounding with a decrease in pathway activity. These pathways have already been suggested to play a role in keloid disease, and our analysis provides further evidence to support their involvement (Bagabir et al, 2011;Syed and Bayat, 2012;Wu et al, 2017). Moreover, DNA repair and p53 signaling pathways were also highlighted (Yamauchi et al, 2018).…”

“…This analysis identified the mitogen-activated protein kinase signaling pathway as the only gene set to be significantly dysregulated in the keloid prone subjects 6 weeks after wounding (see Supplementary Tables S4, S5 online). Notably, other published data have shown that inhibition of mitogenactivated protein kinase hinders invasive growth of keloid fibroblasts (Wu et al, 2017).…”

Asiaticoside inhibits TGF-β1-induced mesothelial-mesenchymal transition and oxidative stress via the Nrf2/HO-1 signaling pathway in the human peritoneal mesothelial cell line HMrSV5

“…All the above results confirmed that asiaticoside can inhibit MMT via TGF-β/Smad signaling. Earlier studies have revealed the anti-MMT effect of asiaticoside in keloid fibroblasts and lung epithelial cells [14]. However, there have been no reports in the context of PD.…”

“…Asiaticoside (shown in Fig.1) is the main component of triterpenoid saponins extracted from Centella asiatica with a clear formula. Emerging evidence has indicated that asiaticoside shows antioxidant, antiinflammatory, anti-fibrotic and other pharmacological effects [14][15][16]. In the PD field, the protective effects of asiaticoside against MMT and PD-related ROS remain unknown.…”

Systemic factors that shape cutaneous pathological scarring

“…Other possibilities are onion extract and asiaticoside (a triterpenoid from a herb called Centella asiatica), which have already been used widely to treat keloids. [91][92][93] Another possibility is trace elements such as copper and zinc, which are known to play essential roles in wound healing 94 and/or fibrosis. 95 However, Bang and Dashti did not find any evidence that changes in these elements (eg, zinc, copper, manganese, and selenium) contribute to cutaneous pathological scarring.…”