Diminished Vitamin D Receptor Protein Levels in Crohn’s Disease Fibroblasts: Effects of Vitamin D

Vitamin D (VD) deficiency has been associated to Crohn’s disease (CD) pathogenesis, and the exogenous administration of VD improves the course of the disease, but the mechanistic basis of these observations remains unknown. Vitamin D receptor (VDR) mediates most of the biological functions of this h...

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Detalhes bibliográficos
Autores: Gisbert Ferrándiz, Laura, Cosín-Roger, Jesús, Hernández, Carlos, Macias-Ceja, Dulce C., Ortiz-Masiá, Dolores, Salvador, Pedro, Esplugues, Juan V., Hinojosa, Joaquín, Navarro, Francisco, Calatayud, Sara, Barrachina, María D.
Tipo de documento: artigo
Data de publicação:2020
País:España
Recursos:Universidad Católica de Valencia San Vicente Mártir
Repositório:RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
Idioma:inglês
OAI Identifier:oai:riucv.ucv.es:20.500.12466/7543
Acesso em linha:https://hdl.handle.net/20.500.12466/7543
Access Level:Acceso aberto
Palavra-chave:Crohn’s disease
Vitamin D
Vitamin D receptor (VDR)
Fibroblasts
Fibrosis
32 Ciencias Médicas
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spelling Diminished Vitamin D Receptor Protein Levels in Crohn’s Disease Fibroblasts: Effects of Vitamin DGisbert Ferrándiz, LauraCosín-Roger, JesúsHernández, CarlosMacias-Ceja, Dulce C.Ortiz-Masiá, DoloresSalvador, PedroEsplugues, Juan V.Hinojosa, JoaquínNavarro, FranciscoCalatayud, SaraBarrachina, María D.Crohn’s diseaseVitamin DVitamin D receptor (VDR)FibroblastsFibrosis32 Ciencias MédicasVitamin D (VD) deficiency has been associated to Crohn’s disease (CD) pathogenesis, and the exogenous administration of VD improves the course of the disease, but the mechanistic basis of these observations remains unknown. Vitamin D receptor (VDR) mediates most of the biological functions of this hormone, and we aim to analyze here the expression of VDR in intestinal tissue, epithelial cells, and fibroblasts from CD patients. The e ects of VD on a fibroblast wound healing assay and murine intestinal fibrosis are also analyzed. Our data show diminished VDR protein levels in surgical resections and epithelial cells from CD patients. In intestinal fibroblasts isolated from damaged tissue of CD patients, we detected enhanced migration and decreased VDR expression compared with both fibroblasts from non-damaged tissue of the same CD patient or control fibroblasts. Treatment with VD increased VDR protein levels, avoided the accelerated migration in CD fibroblasts, and prevented murine intestinal fibrosis induced by the heterotopic transplant model. In conclusion, our study demonstrates diminished VDR protein levels associated with enhanced migration in intestinal fibroblasts from damaged tissue of CD patients. In these cells, VD accumulates VDR and normalizes migration, which supports that CD patients would benefit from the VD anti-fibrotic therapeutic value that we demonstrate in a murine experimental model.20262026-02-1920202020-04-0120202020-04-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.12466/7543reponame:RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártirinstname:Universidad Católica de Valencia San Vicente MártirInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:riucv.ucv.es:20.500.12466/75432026-06-19T08:32:07Z
dc.title.none.fl_str_mv Diminished Vitamin D Receptor Protein Levels in Crohn’s Disease Fibroblasts: Effects of Vitamin D
title Diminished Vitamin D Receptor Protein Levels in Crohn’s Disease Fibroblasts: Effects of Vitamin D
spellingShingle Diminished Vitamin D Receptor Protein Levels in Crohn’s Disease Fibroblasts: Effects of Vitamin D
Gisbert Ferrándiz, Laura
Crohn’s disease
Vitamin D
Vitamin D receptor (VDR)
Fibroblasts
Fibrosis
32 Ciencias Médicas
title_short Diminished Vitamin D Receptor Protein Levels in Crohn’s Disease Fibroblasts: Effects of Vitamin D
title_full Diminished Vitamin D Receptor Protein Levels in Crohn’s Disease Fibroblasts: Effects of Vitamin D
title_fullStr Diminished Vitamin D Receptor Protein Levels in Crohn’s Disease Fibroblasts: Effects of Vitamin D
title_full_unstemmed Diminished Vitamin D Receptor Protein Levels in Crohn’s Disease Fibroblasts: Effects of Vitamin D
title_sort Diminished Vitamin D Receptor Protein Levels in Crohn’s Disease Fibroblasts: Effects of Vitamin D
dc.creator.none.fl_str_mv Gisbert Ferrándiz, Laura
Cosín-Roger, Jesús
Hernández, Carlos
Macias-Ceja, Dulce C.
Ortiz-Masiá, Dolores
Salvador, Pedro
Esplugues, Juan V.
Hinojosa, Joaquín
Navarro, Francisco
Calatayud, Sara
Barrachina, María D.
author Gisbert Ferrándiz, Laura
author_facet Gisbert Ferrándiz, Laura
Cosín-Roger, Jesús
Hernández, Carlos
Macias-Ceja, Dulce C.
Ortiz-Masiá, Dolores
Salvador, Pedro
Esplugues, Juan V.
Hinojosa, Joaquín
Navarro, Francisco
Calatayud, Sara
Barrachina, María D.
author_role author
author2 Cosín-Roger, Jesús
Hernández, Carlos
Macias-Ceja, Dulce C.
Ortiz-Masiá, Dolores
Salvador, Pedro
Esplugues, Juan V.
Hinojosa, Joaquín
Navarro, Francisco
Calatayud, Sara
Barrachina, María D.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Crohn’s disease
Vitamin D
Vitamin D receptor (VDR)
Fibroblasts
Fibrosis
32 Ciencias Médicas
topic Crohn’s disease
Vitamin D
Vitamin D receptor (VDR)
Fibroblasts
Fibrosis
32 Ciencias Médicas
description Vitamin D (VD) deficiency has been associated to Crohn’s disease (CD) pathogenesis, and the exogenous administration of VD improves the course of the disease, but the mechanistic basis of these observations remains unknown. Vitamin D receptor (VDR) mediates most of the biological functions of this hormone, and we aim to analyze here the expression of VDR in intestinal tissue, epithelial cells, and fibroblasts from CD patients. The e ects of VD on a fibroblast wound healing assay and murine intestinal fibrosis are also analyzed. Our data show diminished VDR protein levels in surgical resections and epithelial cells from CD patients. In intestinal fibroblasts isolated from damaged tissue of CD patients, we detected enhanced migration and decreased VDR expression compared with both fibroblasts from non-damaged tissue of the same CD patient or control fibroblasts. Treatment with VD increased VDR protein levels, avoided the accelerated migration in CD fibroblasts, and prevented murine intestinal fibrosis induced by the heterotopic transplant model. In conclusion, our study demonstrates diminished VDR protein levels associated with enhanced migration in intestinal fibroblasts from damaged tissue of CD patients. In these cells, VD accumulates VDR and normalizes migration, which supports that CD patients would benefit from the VD anti-fibrotic therapeutic value that we demonstrate in a murine experimental model.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-04-01
2020
2020-04-01
2026
2026-02-19
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/20.500.12466/7543
url https://hdl.handle.net/20.500.12466/7543
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.source.none.fl_str_mv reponame:RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
instname:Universidad Católica de Valencia San Vicente Mártir
instname_str Universidad Católica de Valencia San Vicente Mártir
reponame_str RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
collection RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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