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Prokineticin receptor-1 signaling promotes Epicardial to Mesenchymal Transition during heart development

The epicardium plays an essential role in coronary artery formation and myocardial development. However, signals controlling the developing epicardium and epicardial-mesenchymal transition (EMT) in the normal and diseased adult heart are studied less rigorously. Here we investigated the role of angi...

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Autores principales: Arora, Himanshu, Boulberdaa, Mounia, Qureshi, Rehana, Bitirim, Verda, Gasser, Adeline, Messaddeq, Nadia, Dolle, Pascal, Nebigil, Canan G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4858698/
https://www.ncbi.nlm.nih.gov/pubmed/27150455
http://dx.doi.org/10.1038/srep25541
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author Arora, Himanshu
Boulberdaa, Mounia
Qureshi, Rehana
Bitirim, Verda
Gasser, Adeline
Messaddeq, Nadia
Dolle, Pascal
Nebigil, Canan G.
author_facet Arora, Himanshu
Boulberdaa, Mounia
Qureshi, Rehana
Bitirim, Verda
Gasser, Adeline
Messaddeq, Nadia
Dolle, Pascal
Nebigil, Canan G.
author_sort Arora, Himanshu
collection PubMed
description The epicardium plays an essential role in coronary artery formation and myocardial development. However, signals controlling the developing epicardium and epicardial-mesenchymal transition (EMT) in the normal and diseased adult heart are studied less rigorously. Here we investigated the role of angiogenic hormone, prokineticin-2 and its receptor PKR1 in the epicardium of developing and adult heart. Genetic ablation of PKR1 in epicardium leads to partial embryonic and postnatal lethality with abnormal heart development. Cardiac developmental defects are manifested in the adult stage as ischemic cardiomyopathy with systolic dysfunction. We discovered that PKR1 regulates epicardial-mesenchymal transition (EMT) for epicardial-derived progenitor cell (EPDC), formation. This event affects at least three consequential steps during heart development: (i) EPDC and cardiomyocyte proliferation involved in thickening of an outer compact ventricular chamber wall, (ii) rhythmicity, (iii) formation of coronary circulation. In isolated embryonic EPDCs, overexpression or activation of PKR1 alters cell morphology and EMT markers via activating Akt signaling. Lack of PKR1 signal in epicardium leads to defective heart development and underlies the origin of congenital heart disease in adult mice. Our mice provide genetic models for congenital dysfunction of the heart and should facilitate studies of both pathogenesis and therapy of cardiac disorders in humans.
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spelling pubmed-48586982016-05-19 Prokineticin receptor-1 signaling promotes Epicardial to Mesenchymal Transition during heart development Arora, Himanshu Boulberdaa, Mounia Qureshi, Rehana Bitirim, Verda Gasser, Adeline Messaddeq, Nadia Dolle, Pascal Nebigil, Canan G. Sci Rep Article The epicardium plays an essential role in coronary artery formation and myocardial development. However, signals controlling the developing epicardium and epicardial-mesenchymal transition (EMT) in the normal and diseased adult heart are studied less rigorously. Here we investigated the role of angiogenic hormone, prokineticin-2 and its receptor PKR1 in the epicardium of developing and adult heart. Genetic ablation of PKR1 in epicardium leads to partial embryonic and postnatal lethality with abnormal heart development. Cardiac developmental defects are manifested in the adult stage as ischemic cardiomyopathy with systolic dysfunction. We discovered that PKR1 regulates epicardial-mesenchymal transition (EMT) for epicardial-derived progenitor cell (EPDC), formation. This event affects at least three consequential steps during heart development: (i) EPDC and cardiomyocyte proliferation involved in thickening of an outer compact ventricular chamber wall, (ii) rhythmicity, (iii) formation of coronary circulation. In isolated embryonic EPDCs, overexpression or activation of PKR1 alters cell morphology and EMT markers via activating Akt signaling. Lack of PKR1 signal in epicardium leads to defective heart development and underlies the origin of congenital heart disease in adult mice. Our mice provide genetic models for congenital dysfunction of the heart and should facilitate studies of both pathogenesis and therapy of cardiac disorders in humans. Nature Publishing Group 2016-05-06 /pmc/articles/PMC4858698/ /pubmed/27150455 http://dx.doi.org/10.1038/srep25541 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Arora, Himanshu
Boulberdaa, Mounia
Qureshi, Rehana
Bitirim, Verda
Gasser, Adeline
Messaddeq, Nadia
Dolle, Pascal
Nebigil, Canan G.
Prokineticin receptor-1 signaling promotes Epicardial to Mesenchymal Transition during heart development
title Prokineticin receptor-1 signaling promotes Epicardial to Mesenchymal Transition during heart development
title_full Prokineticin receptor-1 signaling promotes Epicardial to Mesenchymal Transition during heart development
title_fullStr Prokineticin receptor-1 signaling promotes Epicardial to Mesenchymal Transition during heart development
title_full_unstemmed Prokineticin receptor-1 signaling promotes Epicardial to Mesenchymal Transition during heart development
title_short Prokineticin receptor-1 signaling promotes Epicardial to Mesenchymal Transition during heart development
title_sort prokineticin receptor-1 signaling promotes epicardial to mesenchymal transition during heart development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4858698/
https://www.ncbi.nlm.nih.gov/pubmed/27150455
http://dx.doi.org/10.1038/srep25541
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