CCBE1 Is Essential for Epicardial Function during Myocardium Development

Detalhes bibliográficos
Autor(a) principal: Bonet, Fernando
Data de Publicação: 2022
Outros Autores: Añez, Sabrina Brito, Inácio, José Manuel, Futschik, Matthias E., Belo, José Antonio
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/145250
Resumo: Funding: This work was supported by Fundação para a Ciência e a Tecnologia (FCT) grants (PTDC/MEC-CAR/29590/2017) to JA Belo and by the Scientific Employment Stimulus to JMI (Norma Transitória 8189/2018, FCT), and iNOVA4Health—UIDB/Multi/04462/2013, a program Int. J. Mol. Sci. 2022, 23, 12642 14 of 17 financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement.
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spelling CCBE1 Is Essential for Epicardial Function during Myocardium DevelopmentCCBE1EMTepicardial derived cellsepicardiumheart developmentmyocardial growthCatalysisMolecular BiologySpectroscopyComputer Science ApplicationsPhysical and Theoretical ChemistryOrganic ChemistryInorganic ChemistryFunding: This work was supported by Fundação para a Ciência e a Tecnologia (FCT) grants (PTDC/MEC-CAR/29590/2017) to JA Belo and by the Scientific Employment Stimulus to JMI (Norma Transitória 8189/2018, FCT), and iNOVA4Health—UIDB/Multi/04462/2013, a program Int. J. Mol. Sci. 2022, 23, 12642 14 of 17 financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement.The epicardium is a single cell layer of mesothelial cells that plays a critical role during heart development contributing to different cardiac cell types of the developing heart through epithelial-to-mesenchymal transition (EMT). Moreover, the epicardium is a source of secreted growth factors that promote myocardial growth. CCBE1 is a secreted extracellular matrix protein expressed by epicardial cells that is required for the formation of the primitive coronary plexus. However, the role of CCBE1 during epicardial development was still unknown. Here, using a Ccbe1 knockout (KO) mouse model, we observed that loss of CCBE1 leads to congenital heart defects including thinner and hyper-trabeculated ventricular myocardium. In addition, Ccbe1 mutant hearts displayed reduced proliferation of cardiomyocyte and epicardial cells. Epicardial outgrowth culture assay to assess epicardial-derived cells (EPDC) migration showed reduced invasion of the collagen gel by EPDCs in Ccbe1 KO epicardial explants. Ccbe1 KO hearts also displayed fewer nonmyocyte/nonendothelial cells intramyocardially with a reduced proliferation rate. Additionally, RNA-seq data and experimental validation by qRT-PCR showed a marked deregulation of EMT-related genes in developing Ccbe1 mutant hearts. Together, these findings indicate that the myocardium defects in Ccbe1 KO mice arise from disruption of epicardial development and function.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNBonet, FernandoAñez, Sabrina BritoInácio, José ManuelFutschik, Matthias E.Belo, José Antonio2022-11-04T22:11:22Z2022-10-202022-10-20T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/145250eng1422-0067PURE: 47564377https://doi.org/10.3390/ijms232012642info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:25:26Zoai:run.unl.pt:10362/145250Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:51:58.967469Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv CCBE1 Is Essential for Epicardial Function during Myocardium Development
title CCBE1 Is Essential for Epicardial Function during Myocardium Development
spellingShingle CCBE1 Is Essential for Epicardial Function during Myocardium Development
Bonet, Fernando
CCBE1
EMT
epicardial derived cells
epicardium
heart development
myocardial growth
Catalysis
Molecular Biology
Spectroscopy
Computer Science Applications
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry
title_short CCBE1 Is Essential for Epicardial Function during Myocardium Development
title_full CCBE1 Is Essential for Epicardial Function during Myocardium Development
title_fullStr CCBE1 Is Essential for Epicardial Function during Myocardium Development
title_full_unstemmed CCBE1 Is Essential for Epicardial Function during Myocardium Development
title_sort CCBE1 Is Essential for Epicardial Function during Myocardium Development
author Bonet, Fernando
author_facet Bonet, Fernando
Añez, Sabrina Brito
Inácio, José Manuel
Futschik, Matthias E.
Belo, José Antonio
author_role author
author2 Añez, Sabrina Brito
Inácio, José Manuel
Futschik, Matthias E.
Belo, José Antonio
author2_role author
author
author
author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
RUN
dc.contributor.author.fl_str_mv Bonet, Fernando
Añez, Sabrina Brito
Inácio, José Manuel
Futschik, Matthias E.
Belo, José Antonio
dc.subject.por.fl_str_mv CCBE1
EMT
epicardial derived cells
epicardium
heart development
myocardial growth
Catalysis
Molecular Biology
Spectroscopy
Computer Science Applications
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry
topic CCBE1
EMT
epicardial derived cells
epicardium
heart development
myocardial growth
Catalysis
Molecular Biology
Spectroscopy
Computer Science Applications
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry
description Funding: This work was supported by Fundação para a Ciência e a Tecnologia (FCT) grants (PTDC/MEC-CAR/29590/2017) to JA Belo and by the Scientific Employment Stimulus to JMI (Norma Transitória 8189/2018, FCT), and iNOVA4Health—UIDB/Multi/04462/2013, a program Int. J. Mol. Sci. 2022, 23, 12642 14 of 17 financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement.
publishDate 2022
dc.date.none.fl_str_mv 2022-11-04T22:11:22Z
2022-10-20
2022-10-20T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/145250
url http://hdl.handle.net/10362/145250
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1422-0067
PURE: 47564377
https://doi.org/10.3390/ijms232012642
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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