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Pharmacological activation of estrogen receptors-α and -β differentially modulates keratinocyte differentiation with functional impact on wound healing

  • Authors:
    • Vlasta Peržeľová
    • František Sabol
    • Tomáš Vasilenko
    • Martin Novotný
    • Ivan Kováč
    • Martin Slezák
    • Ján Ďurkáč
    • Martin Hollý
    • Martina Pilátová
    • Pavol Szabo
    • Lenka Varinská
    • Zuzana Čriepoková
    • Tomáš Kučera
    • Herbert Kaltner
    • Sabine André
    • Hans‑Joachim Gabius
    • Pavel Mučaji
    • Karel Smetana
    • Peter Gál
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, Košice, Slovak Republic, Department of Heart Surgery, East‑Slovak Institute of Cardiovascular Diseases and Pavol Jozef Šafárik University, Košice, Slovak Republic, Department of Surgery, Košice‑Šaca Hospital and Pavol Jozef Šafárik University, Košice, Slovak Republic, Department for Biomedical Research, East‑Slovak Institute of Cardiovascular Diseases, Košice, Slovak Republic, Department of Pathological Anatomy and Physiology, University of Veterinary Medicine and Pharmacy, Košice, Slovak Republic, Institute of Anatomy, First Faculty of Medicine, Charles University, Prague, Czech Republic, Institute of Histology and Embryology, First Faculty of Medicine, Charles University, Prague, Czech Republic, Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig‑Maximilians‑University Munich, Munich, Germany, Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University, Bratislava, Slovak Republic
    Copyright: © Peržeľová et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 21-28
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    Published online on: September 21, 2015
       https://doi.org/10.3892/ijmm.2015.2351
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Abstract

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.
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Copy and paste a formatted citation
Spandidos Publications style
Peržeľová V, Sabol F, Vasilenko T, Novotný M, Kováč I, Slezák M, Ďurkáč J, Hollý M, Pilátová M, Szabo P, Szabo P, et al: Pharmacological activation of estrogen receptors-α and -β differentially modulates keratinocyte differentiation with functional impact on wound healing. Int J Mol Med 37: 21-28, 2016.
APA
Peržeľová, V., Sabol, F., Vasilenko, T., Novotný, M., Kováč, I., Slezák, M. ... Gál, P. (2016). Pharmacological activation of estrogen receptors-α and -β differentially modulates keratinocyte differentiation with functional impact on wound healing. International Journal of Molecular Medicine, 37, 21-28. https://doi.org/10.3892/ijmm.2015.2351
MLA
Peržeľová, V., Sabol, F., Vasilenko, T., Novotný, M., Kováč, I., Slezák, M., Ďurkáč, J., Hollý, M., Pilátová, M., Szabo, P., Varinská, L., Čriepoková, Z., Kučera, T., Kaltner, H., André, S., Gabius, H., Mučaji, P., Smetana, K., Gál, P."Pharmacological activation of estrogen receptors-α and -β differentially modulates keratinocyte differentiation with functional impact on wound healing". International Journal of Molecular Medicine 37.1 (2016): 21-28.
Chicago
Peržeľová, V., Sabol, F., Vasilenko, T., Novotný, M., Kováč, I., Slezák, M., Ďurkáč, J., Hollý, M., Pilátová, M., Szabo, P., Varinská, L., Čriepoková, Z., Kučera, T., Kaltner, H., André, S., Gabius, H., Mučaji, P., Smetana, K., Gál, P."Pharmacological activation of estrogen receptors-α and -β differentially modulates keratinocyte differentiation with functional impact on wound healing". International Journal of Molecular Medicine 37, no. 1 (2016): 21-28. https://doi.org/10.3892/ijmm.2015.2351
Copy and paste a formatted citation
x
Spandidos Publications style
Peržeľová V, Sabol F, Vasilenko T, Novotný M, Kováč I, Slezák M, Ďurkáč J, Hollý M, Pilátová M, Szabo P, Szabo P, et al: Pharmacological activation of estrogen receptors-α and -β differentially modulates keratinocyte differentiation with functional impact on wound healing. Int J Mol Med 37: 21-28, 2016.
APA
Peržeľová, V., Sabol, F., Vasilenko, T., Novotný, M., Kováč, I., Slezák, M. ... Gál, P. (2016). Pharmacological activation of estrogen receptors-α and -β differentially modulates keratinocyte differentiation with functional impact on wound healing. International Journal of Molecular Medicine, 37, 21-28. https://doi.org/10.3892/ijmm.2015.2351
MLA
Peržeľová, V., Sabol, F., Vasilenko, T., Novotný, M., Kováč, I., Slezák, M., Ďurkáč, J., Hollý, M., Pilátová, M., Szabo, P., Varinská, L., Čriepoková, Z., Kučera, T., Kaltner, H., André, S., Gabius, H., Mučaji, P., Smetana, K., Gál, P."Pharmacological activation of estrogen receptors-α and -β differentially modulates keratinocyte differentiation with functional impact on wound healing". International Journal of Molecular Medicine 37.1 (2016): 21-28.
Chicago
Peržeľová, V., Sabol, F., Vasilenko, T., Novotný, M., Kováč, I., Slezák, M., Ďurkáč, J., Hollý, M., Pilátová, M., Szabo, P., Varinská, L., Čriepoková, Z., Kučera, T., Kaltner, H., André, S., Gabius, H., Mučaji, P., Smetana, K., Gál, P."Pharmacological activation of estrogen receptors-α and -β differentially modulates keratinocyte differentiation with functional impact on wound healing". International Journal of Molecular Medicine 37, no. 1 (2016): 21-28. https://doi.org/10.3892/ijmm.2015.2351
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