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

Troncoso, Felipe; Herlitz, Kurt; Acurio, Jesenia; Aguayo, Claudio; Guevara, Katherine; Castro, Fidel Ovidio; Godoy, Alejandro S.; San Martin, Sebastian; Escudero, Carlos

doi:10.3390/ijms21197145

Open AccessArticle

Advantages in Wound Healing Process in Female Mice Require Upregulation A_2A-Mediated Angiogenesis under the Stimulation of 17β-Estradiol

by

Felipe Troncoso

^1,2,

Kurt Herlitz

¹,

Jesenia Acurio

^1,3,

Claudio Aguayo

^3,4

,

Katherine Guevara

¹,

Fidel Ovidio Castro

⁵

,

Alejandro S. Godoy

^3,6,7,

Sebastian San Martin

^3,8 and

Carlos Escudero

^1,3,*

¹

Vascular Physiology Laboratory, Department of Basic Sciences, Universidad del Bío-Bío, 3780000 Chillán, Chile

²

Programa de Doctorado en Ciencias Veterinarias, Universidad de Concepción, 3780000 Chillán, Chile

³

Group of Research and Innovation in Vascular Health (GRIVAS Health), 3780000 Chillán, Chile

⁴

Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, 4030000 Concepción, Chile

⁵

Department of Animal Science, Faculty of Veterinary Sciences, Universidad de Concepcion, 3780000 Chillán, Chile

⁶

Department of Urology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA

⁷

Centro de Biología Celular y Biomedicina (CEBICEM), Universidad San Sebastián, 8320000 Santiago, Chile

⁸

Biomedical Research Centre, School of Medicine, Universidad de Valparaíso, 2340000 Valparaíso, Chile

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2020, 21(19), 7145; https://doi.org/10.3390/ijms21197145

Submission received: 26 July 2020 / Revised: 12 August 2020 / Accepted: 25 August 2020 / Published: 28 September 2020

(This article belongs to the Section Molecular Endocrinology and Metabolism)

Download

Browse Figures

Review Reports Versions Notes

Abstract

Estrogenic steroids and adenosine A_2A 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 A_2A receptors. Using in vivo analyses, we showed that female wild type (WT) mice have a more rapid wound healing process than female or male A_2A-deficient mice (A_2AKO) mice. We also found that pulmonary endothelial cells (mPEC) isolated from female WT mice showed higher expression of A_2A receptor than mPEC from male WT mice. mPEC from female WT mice were more sensitive to A_2A-mediated pro-angiogenic response, suggesting an ER and A_2A crosstalk, which was confirmed using cells isolated from A_2AKO. In those female cells, 17β-estradiol potentiated A_2A-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 A_2A adenosine receptors, likely involving activation of ERα and ERβ receptors. Sexual dimorphism in wound healing observed in the A_2AKO mice process reinforces the functional crosstalk between ER and A_2A receptors.

Keywords: adenosine; A_2A receptor; angiogenesis; wound healing

Share and Cite

MDPI and ACS Style

Troncoso, F.; Herlitz, K.; Acurio, J.; Aguayo, C.; Guevara, K.; Castro, F.O.; Godoy, A.S.; San Martin, S.; Escudero, C. Advantages in Wound Healing Process in Female Mice Require Upregulation A_2A-Mediated Angiogenesis under the Stimulation of 17β-Estradiol. Int. J. Mol. Sci. 2020, 21, 7145. https://doi.org/10.3390/ijms21197145

AMA Style

Troncoso F, Herlitz K, Acurio J, Aguayo C, Guevara K, Castro FO, Godoy AS, San Martin S, Escudero C. Advantages in Wound Healing Process in Female Mice Require Upregulation A_2A-Mediated Angiogenesis under the Stimulation of 17β-Estradiol. International Journal of Molecular Sciences. 2020; 21(19):7145. https://doi.org/10.3390/ijms21197145

Chicago/Turabian Style

Troncoso, Felipe, Kurt Herlitz, Jesenia Acurio, Claudio Aguayo, Katherine Guevara, Fidel Ovidio Castro, Alejandro S. Godoy, Sebastian San Martin, and Carlos Escudero. 2020. "Advantages in Wound Healing Process in Female Mice Require Upregulation A_2A-Mediated Angiogenesis under the Stimulation of 17β-Estradiol" International Journal of Molecular Sciences 21, no. 19: 7145. https://doi.org/10.3390/ijms21197145

APA Style

Troncoso, F., Herlitz, K., Acurio, J., Aguayo, C., Guevara, K., Castro, F. O., Godoy, A. S., San Martin, S., & Escudero, C. (2020). Advantages in Wound Healing Process in Female Mice Require Upregulation A_2A-Mediated Angiogenesis under the Stimulation of 17β-Estradiol. International Journal of Molecular Sciences, 21(19), 7145. https://doi.org/10.3390/ijms21197145

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

Advantages in Wound Healing Process in Female Mice Require Upregulation A_2A-Mediated Angiogenesis under the Stimulation of 17β-Estradiol

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI