Reelin expression is up-regulated in mice colon in response to acute colitis and provides resistance against colitis

Reelin is an extracellular matrix protein first known for its key role in neuronal migration. Studies in rodent small intestine suggested that reelin protects the organism from intestinal pathology. Here we determined in mice colon, by real time-PCR and immunological assays, the expression of the re...

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Autores: Carvajal Vázquez, Ana Eloisa, Vázquez Carretero, María Dolores, García Miranda, Pablo, Peral Rubio, María José, Calonge Castrillo, María Luisa, Ilundáin Larrañeta, María Anunciación Ana
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2017
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/85340
Acceso en línea:https://hdl.handle.net/11441/85340
https://doi.org/10.1016/j.bbadis.2016.11.028
Access Level:acceso abierto
Palabra clave:Colon
DNMT1
DSS-colitis
Reelin
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spelling Reelin expression is up-regulated in mice colon in response to acute colitis and provides resistance against colitisCarvajal Vázquez, Ana EloisaVázquez Carretero, María DoloresGarcía Miranda, PabloPeral Rubio, María JoséCalonge Castrillo, María LuisaIlundáin Larrañeta, María Anunciación AnaColonDNMT1DSS-colitisReelinReelin is an extracellular matrix protein first known for its key role in neuronal migration. Studies in rodent small intestine suggested that reelin protects the organism from intestinal pathology. Here we determined in mice colon, by real time-PCR and immunological assays, the expression of the reelin signalling system; its response to dextran sulphate sodium (DSS) and the response of wild-type and reeler mice to DSS-treatment. DNA methylation was determined by bisulfite modification and sequencing of genomic DNA. In the colon mucosa reelin expression is restricted to the myofibroblasts, whereas both epithelial cells and myofibroblasts express reelin receptors (ApoER2 and VLDLR) and its effector protein Dab1. The muscle layer also expresses reelin. DSS-treatment reduces reelin expression in the muscle but it is activated in the mucosa. Activation of mucosal reelin is greater in magnitude and is delayed until after the activation of the myofibroblasts marker, α-SMA. This indicates that the DSS-induced reelin up-regulation results from changes in the reelin gene expression rather than from myofibroblasts proliferation. DSS-treatment does not modify Sp1 or Tbr1 mRNA abundance, but increases that of TGF-β1 and ApoER2, decreases that of CASK and DNMT1 and it also decreases the reelin promoter methylation. Finally, the reeler mice exhibit higher inflammatory scores than wild-type mice, indicating that the mutation increases the susceptibility to DSS-colitis. In summary, this data are the first to demonstrate that mouse distal colon increases reelin production in response to DSS-colitis via a DNMT1-dependent hypo-methylation of the gene promoter region and that reelin provides protection against colitisEspaña, Junta de Andalucía CTS 5884Elsevier2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/85340https://doi.org/10.1016/j.bbadis.2016.11.028reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésBiochimica et Biophysica Acta Molecular and Cell Biology of Lipids, 1863 (2), 462-473.CTS 5884http://dx.doi.org/10.1016/j.bbadis.2016.11.028info:eu-repo/semantics/openAccessoai:idus.us.es:11441/853402026-06-17T12:51:07Z
dc.title.none.fl_str_mv Reelin expression is up-regulated in mice colon in response to acute colitis and provides resistance against colitis
title Reelin expression is up-regulated in mice colon in response to acute colitis and provides resistance against colitis
spellingShingle Reelin expression is up-regulated in mice colon in response to acute colitis and provides resistance against colitis
Carvajal Vázquez, Ana Eloisa
Colon
DNMT1
DSS-colitis
Reelin
title_short Reelin expression is up-regulated in mice colon in response to acute colitis and provides resistance against colitis
title_full Reelin expression is up-regulated in mice colon in response to acute colitis and provides resistance against colitis
title_fullStr Reelin expression is up-regulated in mice colon in response to acute colitis and provides resistance against colitis
title_full_unstemmed Reelin expression is up-regulated in mice colon in response to acute colitis and provides resistance against colitis
title_sort Reelin expression is up-regulated in mice colon in response to acute colitis and provides resistance against colitis
dc.creator.none.fl_str_mv Carvajal Vázquez, Ana Eloisa
Vázquez Carretero, María Dolores
García Miranda, Pablo
Peral Rubio, María José
Calonge Castrillo, María Luisa
Ilundáin Larrañeta, María Anunciación Ana
author Carvajal Vázquez, Ana Eloisa
author_facet Carvajal Vázquez, Ana Eloisa
Vázquez Carretero, María Dolores
García Miranda, Pablo
Peral Rubio, María José
Calonge Castrillo, María Luisa
Ilundáin Larrañeta, María Anunciación Ana
author_role author
author2 Vázquez Carretero, María Dolores
García Miranda, Pablo
Peral Rubio, María José
Calonge Castrillo, María Luisa
Ilundáin Larrañeta, María Anunciación Ana
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Colon
DNMT1
DSS-colitis
Reelin
topic Colon
DNMT1
DSS-colitis
Reelin
description Reelin is an extracellular matrix protein first known for its key role in neuronal migration. Studies in rodent small intestine suggested that reelin protects the organism from intestinal pathology. Here we determined in mice colon, by real time-PCR and immunological assays, the expression of the reelin signalling system; its response to dextran sulphate sodium (DSS) and the response of wild-type and reeler mice to DSS-treatment. DNA methylation was determined by bisulfite modification and sequencing of genomic DNA. In the colon mucosa reelin expression is restricted to the myofibroblasts, whereas both epithelial cells and myofibroblasts express reelin receptors (ApoER2 and VLDLR) and its effector protein Dab1. The muscle layer also expresses reelin. DSS-treatment reduces reelin expression in the muscle but it is activated in the mucosa. Activation of mucosal reelin is greater in magnitude and is delayed until after the activation of the myofibroblasts marker, α-SMA. This indicates that the DSS-induced reelin up-regulation results from changes in the reelin gene expression rather than from myofibroblasts proliferation. DSS-treatment does not modify Sp1 or Tbr1 mRNA abundance, but increases that of TGF-β1 and ApoER2, decreases that of CASK and DNMT1 and it also decreases the reelin promoter methylation. Finally, the reeler mice exhibit higher inflammatory scores than wild-type mice, indicating that the mutation increases the susceptibility to DSS-colitis. In summary, this data are the first to demonstrate that mouse distal colon increases reelin production in response to DSS-colitis via a DNMT1-dependent hypo-methylation of the gene promoter region and that reelin provides protection against colitis
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/85340
https://doi.org/10.1016/j.bbadis.2016.11.028
url https://hdl.handle.net/11441/85340
https://doi.org/10.1016/j.bbadis.2016.11.028
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids, 1863 (2), 462-473.
CTS 5884
http://dx.doi.org/10.1016/j.bbadis.2016.11.028
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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