Epidermal regeneration by ent-16α, 17-dihydroxy-kauran-19-oic acid isolated from Siegesbeckia pubescens
Objectives:
Keratinocyte stem/progenitor cells (KSCs) are known to regenerate epidermal tissue which they perform through to their great regenerative capacity.
Materials And Methods:
Because stimulation of resident KSCs may regenerate epidermal tissue, we devised a strategy to find an appropriate KSC activator from natural products and to develop it as a skin-rejuvenating agent.
Results:
Ent-16α, 17-dihydroxy-kauran-19-oic acid (DHK) isolated from Siegesbeckia pubescens exhibited a KSC-stimulating effect during screening of natural products. DHK increased proliferation and migration of KSCs using the Akt/ERK pathway. We further examined the mechanism of KSC stimulation and found that phosphorylation of Y1068 epithelial growth factor receptor (EGFR) was significantly increased. Functional inhibition of EGFR using neutralizing antibody and a chemical inhibitor, AG1478, attenuated DHK-induced KSC stimulation. In a 3D culture model of KSCs, DHK treatment significantly induced establishment of fully stratified epidermis and increased numbers of p63-positive cells. Likewise, DHK treatment significantly accelerated healing of epidermal wounds created by laser and dermatome, and increased p63-positive cells, in animal models.
Conclusion:
Collectively, these results indicate that DHK regenerates epidermal tissue mainly through EGFR phosphorylation. As DHK has diverse advantages over recombinant growth factors for commercialization (that is long-term stability and skin permeability), DHK might be applied to wound-healing agents and to a basic materials used in cosmetics.
Related Concept Videos
Renewal of Skin Epidermal Stem Cells
Clinical Applications of Epidermal Stem Cells
Overview of Regeneration and Repair
Regeneration
All animals have varying degrees of...
Tissue Renewal without Stem Cells
However, failure of such a system...
Liver Regeneration
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are large...
Whole Body Regeneration


