Estrogen deprivation is considered responsible for many age-related processes, including poor wound healing. Guided by previous observations that estradiol accelerates re‑epithelialization through estrogen receptor (ER)‑β, in the present study, we examined whether selective ER agonists [4,4',4''-(4-propyl [1H] pyrazole-1,3,5-triyl)‑trisphenol (PPT), ER‑α agonist; 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN), ER‑β agonist] affect the expression of basic proliferation and differentiation markers (Ki‑67, keratin‑10, ‑14 and ‑19, galectin‑1 and Sox‑2) of keratinocytes using HaCaT cells. In parallel, ovariectomized rats were treated daily with an ER modulator, and wound tissue was removed 21 days after wounding and routinely processed for basic histological analysis. Our results revealed that the HaCaT keratinocytes expressed both ER‑α and ‑β, and thus are well-suited for studying the effects of ER agonists on epidermal regeneration. The activation of ER‑α produced a protein expression pattern similar to that observed in the control culture, with a moderate expression of Ki‑67 being observed. However, the activation of ER‑β led to an increase in cell proliferation and keratin‑19 expression, as well as a decrease in galectin‑1 expression. Fittingly, in rat wounds treated with the ER‑β agonist (DPN), epidermal regeneration was accelerated. In the present study, we provide information on the mechanisms through which estrogens affect the expression patterns of selected markers, thus modulating keratinocyte proliferation and differentiation; in addition, we demonstrate that the pharmacological activation of ER-α and -β has a direct impact on wound healing.

Department for Biomedical Research East‑Slovak Institute of Cardiovascular Diseases Košice Slovak Republic

Department of Heart Surgery East‑Slovak Institute of Cardiovascular Diseases and Pavol Jozef Šafárik University Košice Slovak Republic

Department of Pathological Anatomy and Physiology University of Veterinary Medicine and Pharmacy Košice Slovak Republic

Department of Pharmacognosy and Botany Faculty of Pharmacy Comenius University Bratislava Slovak Republic

Department of Pharmacology Faculty of Medicine Pavol Jozef Šafárik University Košice Slovak Republic

Department of Surgery Košice‑Šaca Hospital and Pavol Jozef Šafárik University Košice Slovak Republic

Institute of Anatomy 1st Faculty of Medicine Charles University Prague Czech Republic

Institute of Histology and Embryology 1st Faculty of Medicine Charles University Prague Czech Republic

Institute of Physiological Chemistry Faculty of Veterinary Medicine Ludwig‑Maximilians‑University Munich Munich Germany

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Molecular Changes Underlying Genistein Treatment of Wound Healing: A Review

Human galectin‑3: Molecular switch of gene expression in dermal fibroblasts in vitro and of skin collagen organization in open wounds and tensile strength in incisions in vivo