Pharmacological Activation of Estrogen Receptors-α and -β Differentially Modulates Keratinocyte Differentiation with Functional Impact on Wound Healing

The study explored how activating estrogen receptors (ERs) affects keratinocyte behavior and wound healing. It was found that stimulating ER-β, but not ER-α, significantly increased keratinocyte proliferation and altered differentiation. HaCaT keratinocytes, expressing both ER types, were treated with ER-α agonist PPT and ER-β agonist DPN. DPN treatment led to more Ki-67-positive cells, a proliferation marker, and higher keratin-19 levels, indicating less differentiation. Conversely, PPT had no significant effect compared to controls. In an in vivo rat model, ER-β activation with DPN sped up epidermal regeneration during wound healing, while ER-α activation did not. These results suggest that ER-β could be a target for therapies aimed at improving wound healing. The study combined human cell culture and rat model data, but the exact number of subjects was not provided.