A synthetic Isoflavone, DCMF, Promotes Human Keratinocyte Migration by Activating Src/FAK Signaling Pathway

Abstract

Flavonoids are a class of secondary compounds produced by plants that contain various pharmacological properties. Our previous report showed that TMF, trimethoxyisoflavone, provided a good effect on wound healing by inducing keratinocyte migration. In this study, we screened derivatives of TMF for searching better pharmacological effects and found 2',6 Dichloro-7-methoxyisoflavone (DCMF) is better candidate for wound healing agents. We investigate the effects and possible action mechanism of 2',6 Dichloro-7-methoxyisoflavone (DCMF) on wound healing using keratinocyte HaCaT cell line and in excisional wound animal model. We found DCMF markedly increased keratinocyte cell migrations but not proliferation. DCMF induced activation of ERK, AKT and p38 MAPK signaling pathways through Src kinase. We also found DCMF induced secretion of MMP-2 and MMP-9, and partial epithelial-mesenchymal transition (EMT). Finally, effects induced by DCMF were abolished when Src was inhibited. In in vivo excisional wound model, DCMF treated mice showed improvement of wound closure and re-epithelialization. In conclusion, DCMF induces cell migration through activation Src, ERK, AKT, p38 signaling pathway.