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Impaired Expression of Ectonucleotidases in Ectopic and Eutopic Endometrial Tissue Is in Favor of ATP Accumulation in the Tissue Microenvironment in Endometriosis

Endometriosis is a prevalent disease defined by the presence of endometrial tissue outside the uterus. Adenosine triphosphate (ATP), as a proinflammatory molecule, promotes and helps maintain the inflammatory state of endometriosis. Moreover, ATP has a direct influence on the two main symptoms of en...

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Autores principales: Trapero, Carla, Vidal, August, Fernández-Montolí, Maria Eulàlia, Coroleu, Buenaventura, Tresserra, Francesc, Barri, Pere, Gómez de Aranda, Inmaculada, Sévigny, Jean, Ponce, Jordi, Matias-Guiu, Xavier, Martín-Satué, Mireia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888134/
https://www.ncbi.nlm.nih.gov/pubmed/31698766
http://dx.doi.org/10.3390/ijms20225532
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author Trapero, Carla
Vidal, August
Fernández-Montolí, Maria Eulàlia
Coroleu, Buenaventura
Tresserra, Francesc
Barri, Pere
Gómez de Aranda, Inmaculada
Sévigny, Jean
Ponce, Jordi
Matias-Guiu, Xavier
Martín-Satué, Mireia
author_facet Trapero, Carla
Vidal, August
Fernández-Montolí, Maria Eulàlia
Coroleu, Buenaventura
Tresserra, Francesc
Barri, Pere
Gómez de Aranda, Inmaculada
Sévigny, Jean
Ponce, Jordi
Matias-Guiu, Xavier
Martín-Satué, Mireia
author_sort Trapero, Carla
collection PubMed
description Endometriosis is a prevalent disease defined by the presence of endometrial tissue outside the uterus. Adenosine triphosphate (ATP), as a proinflammatory molecule, promotes and helps maintain the inflammatory state of endometriosis. Moreover, ATP has a direct influence on the two main symptoms of endometriosis: infertility and pain. Purinergic signaling, the group of biological responses to extracellular nucleotides such as ATP and nucleosides such as adenosine, is involved in the biology of reproduction and is impaired in pathologies with an inflammatory component such as endometriosis. We have previously demonstrated that ectonucleotidases, the enzymes regulating extracellular ATP levels, are active in non-pathological endometria, with hormone-dependent changes in expression throughout the cycle. In the present study we have focused on the expression of ectonucleotidases by means of immunohistochemistry and in situ activity in eutopic and ectopic endometrial tissue of women with endometriosis, and we compared the results with endometria of women without the disease. We have demonstrated that the axis CD39-CD73 is altered in endometriosis, with loss of CD39 and CD73 expression in deep infiltrating endometriosis, the most severe, and most recurring, endometriosis subtype. Our results indicate that this altered expression of ectonucleotidases in endometriosis boosts ATP accumulation in the tissue microenvironment. An important finding is the identification of the nucleotide pyrophophatase/phosphodiesterase 3 (NPP3) as a new histopathological marker of the disease since we have demonstrated its expression in the stroma only in endometriosis, in both eutopic and ectopic tissue. Therefore, targeting the proteins directly involved in ATP breakdown could be an appropriate approach to consider in the treatment of endometriosis.
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spelling pubmed-68881342019-12-09 Impaired Expression of Ectonucleotidases in Ectopic and Eutopic Endometrial Tissue Is in Favor of ATP Accumulation in the Tissue Microenvironment in Endometriosis Trapero, Carla Vidal, August Fernández-Montolí, Maria Eulàlia Coroleu, Buenaventura Tresserra, Francesc Barri, Pere Gómez de Aranda, Inmaculada Sévigny, Jean Ponce, Jordi Matias-Guiu, Xavier Martín-Satué, Mireia Int J Mol Sci Article Endometriosis is a prevalent disease defined by the presence of endometrial tissue outside the uterus. Adenosine triphosphate (ATP), as a proinflammatory molecule, promotes and helps maintain the inflammatory state of endometriosis. Moreover, ATP has a direct influence on the two main symptoms of endometriosis: infertility and pain. Purinergic signaling, the group of biological responses to extracellular nucleotides such as ATP and nucleosides such as adenosine, is involved in the biology of reproduction and is impaired in pathologies with an inflammatory component such as endometriosis. We have previously demonstrated that ectonucleotidases, the enzymes regulating extracellular ATP levels, are active in non-pathological endometria, with hormone-dependent changes in expression throughout the cycle. In the present study we have focused on the expression of ectonucleotidases by means of immunohistochemistry and in situ activity in eutopic and ectopic endometrial tissue of women with endometriosis, and we compared the results with endometria of women without the disease. We have demonstrated that the axis CD39-CD73 is altered in endometriosis, with loss of CD39 and CD73 expression in deep infiltrating endometriosis, the most severe, and most recurring, endometriosis subtype. Our results indicate that this altered expression of ectonucleotidases in endometriosis boosts ATP accumulation in the tissue microenvironment. An important finding is the identification of the nucleotide pyrophophatase/phosphodiesterase 3 (NPP3) as a new histopathological marker of the disease since we have demonstrated its expression in the stroma only in endometriosis, in both eutopic and ectopic tissue. Therefore, targeting the proteins directly involved in ATP breakdown could be an appropriate approach to consider in the treatment of endometriosis. MDPI 2019-11-06 /pmc/articles/PMC6888134/ /pubmed/31698766 http://dx.doi.org/10.3390/ijms20225532 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Trapero, Carla
Vidal, August
Fernández-Montolí, Maria Eulàlia
Coroleu, Buenaventura
Tresserra, Francesc
Barri, Pere
Gómez de Aranda, Inmaculada
Sévigny, Jean
Ponce, Jordi
Matias-Guiu, Xavier
Martín-Satué, Mireia
Impaired Expression of Ectonucleotidases in Ectopic and Eutopic Endometrial Tissue Is in Favor of ATP Accumulation in the Tissue Microenvironment in Endometriosis
title Impaired Expression of Ectonucleotidases in Ectopic and Eutopic Endometrial Tissue Is in Favor of ATP Accumulation in the Tissue Microenvironment in Endometriosis
title_full Impaired Expression of Ectonucleotidases in Ectopic and Eutopic Endometrial Tissue Is in Favor of ATP Accumulation in the Tissue Microenvironment in Endometriosis
title_fullStr Impaired Expression of Ectonucleotidases in Ectopic and Eutopic Endometrial Tissue Is in Favor of ATP Accumulation in the Tissue Microenvironment in Endometriosis
title_full_unstemmed Impaired Expression of Ectonucleotidases in Ectopic and Eutopic Endometrial Tissue Is in Favor of ATP Accumulation in the Tissue Microenvironment in Endometriosis
title_short Impaired Expression of Ectonucleotidases in Ectopic and Eutopic Endometrial Tissue Is in Favor of ATP Accumulation in the Tissue Microenvironment in Endometriosis
title_sort impaired expression of ectonucleotidases in ectopic and eutopic endometrial tissue is in favor of atp accumulation in the tissue microenvironment in endometriosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888134/
https://www.ncbi.nlm.nih.gov/pubmed/31698766
http://dx.doi.org/10.3390/ijms20225532
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