Effects of the novel compound DK223 ([1E,2E-1,2-Bis(6-methoxy-2H-chromen-3-yl)methylene]hydrazine) on migration and proliferation of human keratinocytes and primary dermal fibroblasts.

Manh Ho,Hyun Kang,Yoongho Lim,Young Kim,Jung Huh,Moonjae Cho

doi:10.3390/ijms150713091

Abstract

Wound healing plays an important role in protecting the human body from external infection. Cell migration and proliferation of keratinocytes and dermal fibroblasts are essential for proper wound healing. Recently, several studies have demonstrated that secondary compounds produced in plants could affect skin cells migration and proliferation. In this study, we identified a novel compound DK223 ([1E,2E-1,2-bis(6-methoxy-2H-chromen-3-yl)methylene]hydrazine) that concomitantly induced human keratinocyte migration and dermal fibroblast proliferation. We evaluated the regulation of epithelial and mesenchymal protein markers, such as E-cadherin and Vimentin, in human keratinocytes, as well as extracellular matrix (ECM) secretion and metalloproteinase families in dermal fibroblasts. DK223 upregulated keratinocyte migration and significantly increased the epithelial marker E-cadherin in a time-dependent manner. We also found that reactive oxygen species (ROS) increased significantly in keratinocytes after 2 h of DK223 exposure, returning to normal levels after 24 h, which indicated that DK223 had an early shock effect on ROS production. DK223 also stimulated fibroblast proliferation, and induced significant secretion of ECM proteins, such as collagen I, III, and fibronectin. In dermal fibroblasts, DK223 treatment induced TGF-β1, which is involved in a signaling pathway that mediates proliferation. In conclusion, DK223 simultaneously induced both keratinocyte migration via ROS production and fibroblast proliferation via TGF-β1 induction.

Highlights

As the outer sheath of the human body, the skin absorbs initial damage from injuries or wounds.Disruption of the normal anatomic structure and loss of organ function lead to the repair process known as wound healing
We examined the hypothesis that the novel compound DK223 ([1E,2E-1,2-bis(6-methoxy-2H-chromen-3-yl)methylene]hydrazine) could induce keratinocyte migration, fibroblast proliferation, anti-wrinkle gene expression, and enhance the regeneration of skin, rather than mediate scar formation
The results showed that DK223 at 2 μM significantly enhanced migration of HaCaT (167%), whereas other concentrations did not produce marked effects (Figure 1A)

Summary

Introduction

Disruption of the normal anatomic structure and loss of organ function lead to the repair process known as wound healing. Wound healing integrates different types of dermal cells and immune cells, such as keratinocytes and dermal fibroblasts, to mediate hemostasis, coagulation, and inflammation [1,2]. Wound healing begins with inflammation and immune cell recruitment to protect tissue from foreign invaders, such as bacteria and viruses. The phase resurfaces the skin by stimulating regeneration and repair through proliferation of fibroblasts, re-epithelialization of keratinocytes, and other mechanisms. Several studies have investigated methods to enhance the regeneration process, which is a specific substitution of the damaged tissue, and to reduce skin repair, which causes fibrosis and scar formation [1]

Methods

Results

Conclusion