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

    Vlasta Peržeľová, František Sabol, Tomáš Vasilenko, Martin Novotný, Ivan Kováč, Martin Slezák, Ján Ďurkáč, Martin Hollý, Martina Pilátová, Pavol Szabó, Lenka Varinská, Zuzana Čriepoková, Tomáš Kučera, Herbert Kaltner, Sabine André, Hans‐Joachim Gabius, Pavel Mučaji, Karel Smetana, Péter Gál
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    Studysummary This study found that the activation of ER‑β increased keratinocyte proliferation and gene expression related to epidermal regeneration, enhancing wound healing in both cell models and rats.
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    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.
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