Advantages in Wound Healing Process in Female Mice Require Upregulation A2A-Mediated Angiogenesis under the Stimulation of 17β-Estradiol

Estrogenic steroids and adenosine A2A receptors promote the wound healing and angiogenesis processes. However, so far, it is unclear whether estrogen may regulate the expression and pro-angiogenic activity of A2A receptors. Using in vivo analyses, we showed that female wild type (WT) mice have a mor...

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Veröffentlicht in:International journal of molecular sciences 2020-09, Vol.21 (19), p.7145
Hauptverfasser: Troncoso, Felipe, Herlitz, Kurt, Acurio, Jesenia, Aguayo, Claudio, Guevara, Katherine, Castro, Fidel Ovidio, Godoy, Alejandro S., San Martin, Sebastian, Escudero, Carlos
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container_issue 19
container_start_page 7145
container_title International journal of molecular sciences
container_volume 21
creator Troncoso, Felipe
Herlitz, Kurt
Acurio, Jesenia
Aguayo, Claudio
Guevara, Katherine
Castro, Fidel Ovidio
Godoy, Alejandro S.
San Martin, Sebastian
Escudero, Carlos
description Estrogenic steroids and adenosine A2A receptors promote the wound healing and angiogenesis processes. However, so far, it is unclear whether estrogen may regulate the expression and pro-angiogenic activity of A2A receptors. Using in vivo analyses, we showed that female wild type (WT) mice have a more rapid wound healing process than female or male A2A-deficient mice (A2AKO) mice. We also found that pulmonary endothelial cells (mPEC) isolated from female WT mice showed higher expression of A2A receptor than mPEC from male WT mice. mPEC from female WT mice were more sensitive to A2A-mediated pro-angiogenic response, suggesting an ER and A2A crosstalk, which was confirmed using cells isolated from A2AKO. In those female cells, 17β-estradiol potentiated A2A-mediated cell proliferation, an effect that was inhibited by selective antagonists of estrogen receptors (ER), ERα, and ERβ. Therefore, estrogen regulates the expression and/or pro-angiogenic activity of A2A adenosine receptors, likely involving activation of ERα and ERβ receptors. Sexual dimorphism in wound healing observed in the A2AKO mice process reinforces the functional crosstalk between ER and A2A receptors.
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subjects 17β-Estradiol
Adenosine
Adenosine A2A receptors
Angiogenesis
Cell growth
Cell proliferation
Crosstalk
Endothelial cells
Estrogen receptors
Estrogens
Rodents
Sexual dimorphism
Steroid hormones
Vascular endothelial growth factor
Wound healing
Xenoestrogens
title Advantages in Wound Healing Process in Female Mice Require Upregulation A2A-Mediated Angiogenesis under the Stimulation of 17β-Estradiol
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