Advantages in Wound Healing Process in Female Mice Require Upregulation A<sub>2A</sub>-Mediated Angiogenesis under the Stimulation of 17β-Estradiol
Estrogenic steroids and adenosine A<sub>2A</sub> 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<sub>2A</sub> receptors. Using in vivo analyses, we sho...
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| Format: | Article |
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/19/7145 |
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| author | Felipe Troncoso Kurt Herlitz Jesenia Acurio Claudio Aguayo Katherine Guevara Fidel Ovidio Castro Alejandro S. Godoy Sebastian San Martin Carlos Escudero |
| author_facet | Felipe Troncoso Kurt Herlitz Jesenia Acurio Claudio Aguayo Katherine Guevara Fidel Ovidio Castro Alejandro S. Godoy Sebastian San Martin Carlos Escudero |
| author_sort | Felipe Troncoso |
| collection | DOAJ |
| description | Estrogenic steroids and adenosine A<sub>2A</sub> 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<sub>2A</sub> 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<sub>2A</sub>-deficient mice (A<sub>2A</sub>KO) mice. We also found that pulmonary endothelial cells (mPEC) isolated from female WT mice showed higher expression of A<sub>2A</sub> receptor than mPEC from male WT mice. mPEC from female WT mice were more sensitive to A<sub>2A</sub>-mediated pro-angiogenic response, suggesting an ER and A<sub>2A</sub> crosstalk, which was confirmed using cells isolated from A<sub>2A</sub>KO. In those female cells, 17β-estradiol potentiated A<sub>2A</sub>-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<sub>2A</sub> adenosine receptors, likely involving activation of ERα and ERβ receptors. Sexual dimorphism in wound healing observed in the A<sub>2A</sub>KO mice process reinforces the functional crosstalk between ER and A<sub>2A</sub> receptors. |
| first_indexed | 2024-03-10T16:00:00Z |
| format | Article |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:00:00Z |
| publishDate | 2020-09-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9ef2544c0ee34618bb48dfdb7c79966f2023-11-20T15:21:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012119714510.3390/ijms21197145Advantages in Wound Healing Process in Female Mice Require Upregulation A<sub>2A</sub>-Mediated Angiogenesis under the Stimulation of 17β-EstradiolFelipe Troncoso0Kurt Herlitz1Jesenia Acurio2Claudio Aguayo3Katherine Guevara4Fidel Ovidio Castro5Alejandro S. Godoy6Sebastian San Martin7Carlos Escudero8Vascular Physiology Laboratory, Department of Basic Sciences, Universidad del Bío-Bío, 3780000 Chillán, ChileVascular Physiology Laboratory, Department of Basic Sciences, Universidad del Bío-Bío, 3780000 Chillán, ChileVascular Physiology Laboratory, Department of Basic Sciences, Universidad del Bío-Bío, 3780000 Chillán, ChileGroup of Research and Innovation in Vascular Health (GRIVAS Health), 3780000 Chillán, ChileVascular Physiology Laboratory, Department of Basic Sciences, Universidad del Bío-Bío, 3780000 Chillán, ChileDepartment of Animal Science, Faculty of Veterinary Sciences, Universidad de Concepcion, 3780000 Chillán, ChileGroup of Research and Innovation in Vascular Health (GRIVAS Health), 3780000 Chillán, ChileGroup of Research and Innovation in Vascular Health (GRIVAS Health), 3780000 Chillán, ChileVascular Physiology Laboratory, Department of Basic Sciences, Universidad del Bío-Bío, 3780000 Chillán, ChileEstrogenic steroids and adenosine A<sub>2A</sub> 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<sub>2A</sub> 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<sub>2A</sub>-deficient mice (A<sub>2A</sub>KO) mice. We also found that pulmonary endothelial cells (mPEC) isolated from female WT mice showed higher expression of A<sub>2A</sub> receptor than mPEC from male WT mice. mPEC from female WT mice were more sensitive to A<sub>2A</sub>-mediated pro-angiogenic response, suggesting an ER and A<sub>2A</sub> crosstalk, which was confirmed using cells isolated from A<sub>2A</sub>KO. In those female cells, 17β-estradiol potentiated A<sub>2A</sub>-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<sub>2A</sub> adenosine receptors, likely involving activation of ERα and ERβ receptors. Sexual dimorphism in wound healing observed in the A<sub>2A</sub>KO mice process reinforces the functional crosstalk between ER and A<sub>2A</sub> receptors.https://www.mdpi.com/1422-0067/21/19/7145adenosineA<sub>2A</sub> receptorangiogenesiswound healing |
| spellingShingle | Felipe Troncoso Kurt Herlitz Jesenia Acurio Claudio Aguayo Katherine Guevara Fidel Ovidio Castro Alejandro S. Godoy Sebastian San Martin Carlos Escudero Advantages in Wound Healing Process in Female Mice Require Upregulation A<sub>2A</sub>-Mediated Angiogenesis under the Stimulation of 17β-Estradiol International Journal of Molecular Sciences adenosine A<sub>2A</sub> receptor angiogenesis wound healing |
| title | Advantages in Wound Healing Process in Female Mice Require Upregulation A<sub>2A</sub>-Mediated Angiogenesis under the Stimulation of 17β-Estradiol |
| title_full | Advantages in Wound Healing Process in Female Mice Require Upregulation A<sub>2A</sub>-Mediated Angiogenesis under the Stimulation of 17β-Estradiol |
| title_fullStr | Advantages in Wound Healing Process in Female Mice Require Upregulation A<sub>2A</sub>-Mediated Angiogenesis under the Stimulation of 17β-Estradiol |
| title_full_unstemmed | Advantages in Wound Healing Process in Female Mice Require Upregulation A<sub>2A</sub>-Mediated Angiogenesis under the Stimulation of 17β-Estradiol |
| title_short | Advantages in Wound Healing Process in Female Mice Require Upregulation A<sub>2A</sub>-Mediated Angiogenesis under the Stimulation of 17β-Estradiol |
| title_sort | advantages in wound healing process in female mice require upregulation a sub 2a sub mediated angiogenesis under the stimulation of 17β estradiol |
| topic | adenosine A<sub>2A</sub> receptor angiogenesis wound healing |
| url | https://www.mdpi.com/1422-0067/21/19/7145 |
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