A synthetic isoflavone, DCMF, promotes human keratinocyte migration by activating Src/FAK signaling pathway

作者:Sophors Phorl; Kim Young Mee; Seo Ga Young; Huh Jung Sik; Lim Yoongho; Koh Dong Soo; Cho Moonjae*
来源:Biochemical and Biophysical Research Communications, 2016, 472(2): 332-338.
DOI:10.1016/j.bbrc.2016.02.106

摘要

Flavonoids are plant secondary compounds with various pharmacological properties. We previously showed that one flavonoid, trimethoxyisoflavone (TMF), could promote wound healing by inducing keratinocyte migration. Here, we screened TMF derivatives for enhanced activity and identified one compound, 2',6 Dichloro-7-methoxyisoflavone (DCMF), as most effective at promoting migration in a scratch wound assay. Using the HaCaT keratinocyte cell line, we found DCMF treatment induced phosphorylation of both FAR and Src, and increased keratinocyte migration. DCMF-induced Src kinase could promote activation of ERR, ART, and p38 signaling pathways, and DCMF-induced secretion of matrix metalloproteinase (MMP)-2 and MMP-9 and partial epithelial mesenchymal transition (EMT), whereas Src inhibition abolished DCMF-induced EMT. Using an in vivo excisional wound model, we observed improved wound closure and re-epithelialization in DCMF-treated mice, as compared to controls. Collectively, our data demonstrate that DCMF induces cell migration and promotes wound healing through activation of Src/FAK, ERK, AKT, and p38 MAPK signaling.