Epithelial CD47 is critical for mucosal repair in the murine intestine in vivo

CD47 is a ubiquitously expressed transmembrane glycoprotein that regulates inflammatory responses and tissue repair. Here, we show that normal mice treated with anti-CD47 anti- bodies, and Cd47-null mice have impaired intestinal mucosal wound healing. Furthermore, intestinal epithelial cell (IEC)-sp...

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Autores: Azcutia Criado, Verónica, Reed, Michelle, Luissint, Anny-Claude, Fan, Shuling, O'Leary, Monique N., Quiros, Miguel, Brazil, Jennifer, Nusrat, Asma, Parkos, Charles A.
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/117141
Acceso en línea:https://hdl.handle.net/20.500.14352/117141
Access Level:acceso abierto
Palabra clave:612
Mucosal repair
Intestinal epithelium
CD47
Inflammation
Fisiología vegetal (Farmacia)
24 Ciencias de la Vida
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oai_identifier_str oai:docta.ucm.es:20.500.14352/117141
network_acronym_str ES
network_name_str España
repository_id_str
spelling Epithelial CD47 is critical for mucosal repair in the murine intestine in vivoAzcutia Criado, VerónicaReed, MichelleLuissint, Anny-ClaudeFan, ShulingO'Leary, Monique N.Quiros, MiguelBrazil, JenniferNusrat, AsmaParkos, Charles A.612Mucosal repairIntestinal epitheliumCD47InflammationFisiología vegetal (Farmacia)24 Ciencias de la VidaCD47 is a ubiquitously expressed transmembrane glycoprotein that regulates inflammatory responses and tissue repair. Here, we show that normal mice treated with anti-CD47 anti- bodies, and Cd47-null mice have impaired intestinal mucosal wound healing. Furthermore, intestinal epithelial cell (IEC)-specific loss of CD47 does not induce spontaneous immune- mediated intestinal barrier disruption but results in defective mucosal repair after biopsy- induced colonic wounding or Dextran Sulfate Sodium (DSS)-induced mucosal damage. In vitro analyses using primary cultures of CD47-deficient murine colonic IEC or human colonoid-derived IEC treated with CD47-blocking antibodies demonstrate impaired epithelial cell migration in wound healing assays. Defective wound repair after CD47 loss is linked to decreased epithelial β1 integrin and focal adhesion signaling, as well as reduced thrombospondin-1 and TGF-β1. These results demonstrate a critical role for IEC-expressed CD47 in regulating mucosal repair and raise important considerations for possible alterations in wound healing secondary to therapeutic targeting of CD47.Nature PortfolioUniversidad Complutense de Madrid20192019-01-0120192019-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/117141reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1171412026-06-02T12:44:21Z
dc.title.none.fl_str_mv Epithelial CD47 is critical for mucosal repair in the murine intestine in vivo
title Epithelial CD47 is critical for mucosal repair in the murine intestine in vivo
spellingShingle Epithelial CD47 is critical for mucosal repair in the murine intestine in vivo
Azcutia Criado, Verónica
612
Mucosal repair
Intestinal epithelium
CD47
Inflammation
Fisiología vegetal (Farmacia)
24 Ciencias de la Vida
title_short Epithelial CD47 is critical for mucosal repair in the murine intestine in vivo
title_full Epithelial CD47 is critical for mucosal repair in the murine intestine in vivo
title_fullStr Epithelial CD47 is critical for mucosal repair in the murine intestine in vivo
title_full_unstemmed Epithelial CD47 is critical for mucosal repair in the murine intestine in vivo
title_sort Epithelial CD47 is critical for mucosal repair in the murine intestine in vivo
dc.creator.none.fl_str_mv Azcutia Criado, Verónica
Reed, Michelle
Luissint, Anny-Claude
Fan, Shuling
O'Leary, Monique N.
Quiros, Miguel
Brazil, Jennifer
Nusrat, Asma
Parkos, Charles A.
author Azcutia Criado, Verónica
author_facet Azcutia Criado, Verónica
Reed, Michelle
Luissint, Anny-Claude
Fan, Shuling
O'Leary, Monique N.
Quiros, Miguel
Brazil, Jennifer
Nusrat, Asma
Parkos, Charles A.
author_role author
author2 Reed, Michelle
Luissint, Anny-Claude
Fan, Shuling
O'Leary, Monique N.
Quiros, Miguel
Brazil, Jennifer
Nusrat, Asma
Parkos, Charles A.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 612
Mucosal repair
Intestinal epithelium
CD47
Inflammation
Fisiología vegetal (Farmacia)
24 Ciencias de la Vida
topic 612
Mucosal repair
Intestinal epithelium
CD47
Inflammation
Fisiología vegetal (Farmacia)
24 Ciencias de la Vida
description CD47 is a ubiquitously expressed transmembrane glycoprotein that regulates inflammatory responses and tissue repair. Here, we show that normal mice treated with anti-CD47 anti- bodies, and Cd47-null mice have impaired intestinal mucosal wound healing. Furthermore, intestinal epithelial cell (IEC)-specific loss of CD47 does not induce spontaneous immune- mediated intestinal barrier disruption but results in defective mucosal repair after biopsy- induced colonic wounding or Dextran Sulfate Sodium (DSS)-induced mucosal damage. In vitro analyses using primary cultures of CD47-deficient murine colonic IEC or human colonoid-derived IEC treated with CD47-blocking antibodies demonstrate impaired epithelial cell migration in wound healing assays. Defective wound repair after CD47 loss is linked to decreased epithelial β1 integrin and focal adhesion signaling, as well as reduced thrombospondin-1 and TGF-β1. These results demonstrate a critical role for IEC-expressed CD47 in regulating mucosal repair and raise important considerations for possible alterations in wound healing secondary to therapeutic targeting of CD47.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-01-01
2019
2019-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/117141
url https://hdl.handle.net/20.500.14352/117141
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Portfolio
publisher.none.fl_str_mv Nature Portfolio
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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