Reelin Protects against Colon Pathology via p53 and May Be a Biomarker for Colon Cancer Progression

Previous observations made in human and mouse colons suggest that reelin protects the colon from pathology. In this study, we evaluated reelin expression during the transition from either colitis or precancerous lesions to colon cancer and tried to elucidate reelin regulation under these transition...

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Autores: Serrano Morales, José Manuel, Vázquez Carretero, María Dolores, García Miranda, Pablo, Carvajal Vázquez, Ana Eloisa, Calonge Castrillo, María Luisa, Ilundáin Larrañeta, María Anunciación Ana, Peral Rubio, María José
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/139336
Acceso en línea:https://hdl.handle.net/11441/139336
https://doi.org/10.3390/biology11101406
Access Level:acceso abierto
Palabra clave:Akt
ApoER2
Colitis
Colon cancer
DNMT-1
p53
Reelin
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spelling Reelin Protects against Colon Pathology via p53 and May Be a Biomarker for Colon Cancer ProgressionSerrano Morales, José ManuelVázquez Carretero, María DoloresGarcía Miranda, PabloCarvajal Vázquez, Ana EloisaCalonge Castrillo, María LuisaIlundáin Larrañeta, María Anunciación AnaPeral Rubio, María JoséAktApoER2ColitisColon cancerDNMT-1p53ReelinPrevious observations made in human and mouse colons suggest that reelin protects the colon from pathology. In this study, we evaluated reelin expression during the transition from either colitis or precancerous lesions to colon cancer and tried to elucidate reelin regulation under these transition processes. Samples of healthy and pathological colons from humans and mice treated with either azoxymethane/dextran sulfate sodium (DSS) or azoxymethane alone were used. The relative abundances of reelin, DNMT-1 and ApoER2 mRNAs were determined by PCR in the colon samples cited above and in the tissue adjacent to mouse colon polyps and adenocarcinomas. In both, humans and mice, reelin mRNA abundance increased significantly in ulcerative colitis and slightly in polyps and decreased in adenomas and adenocarcinomas. Reelin expression was higher in the tissue adjacent to the colon adenocarcinoma and lower in the lesion itself. The reelin expression changes may result, at least in part, from those in DNMT-1 and appear to be independent of ApoER2. Lack of reelin downregulated p-Akt and p53 in healthy colon and prevented their increases in the inflamed colon, whereas it increased GSK-3β in DSS-untreated mice. In conclusion, reelin mRNA abundance depends on the severity of the colon pathology, and its upregulation in response to initial injuries might prevent the beginning of colon cancer, whereas reelin repression favors it. Increased p53 expression and activation may be involved in this protection. We also propose that changes in colon reelin abundance could be used to predict colon pathology progression.Junta de Andalucía CTS 5884, 2021/1123 BIO-144Multidisciplinary Digital Publishing Institute (MDPI)FisiologíaJunta de Andalucía2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/139336https://doi.org/10.3390/biology11101406reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésBiology, 11 (10), 1406.CTS 58842021/1123 BIO-144https://doi.org/10.3390/biology11101406info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1393362026-06-17T12:51:07Z
dc.title.none.fl_str_mv Reelin Protects against Colon Pathology via p53 and May Be a Biomarker for Colon Cancer Progression
title Reelin Protects against Colon Pathology via p53 and May Be a Biomarker for Colon Cancer Progression
spellingShingle Reelin Protects against Colon Pathology via p53 and May Be a Biomarker for Colon Cancer Progression
Serrano Morales, José Manuel
Akt
ApoER2
Colitis
Colon cancer
DNMT-1
p53
Reelin
title_short Reelin Protects against Colon Pathology via p53 and May Be a Biomarker for Colon Cancer Progression
title_full Reelin Protects against Colon Pathology via p53 and May Be a Biomarker for Colon Cancer Progression
title_fullStr Reelin Protects against Colon Pathology via p53 and May Be a Biomarker for Colon Cancer Progression
title_full_unstemmed Reelin Protects against Colon Pathology via p53 and May Be a Biomarker for Colon Cancer Progression
title_sort Reelin Protects against Colon Pathology via p53 and May Be a Biomarker for Colon Cancer Progression
dc.creator.none.fl_str_mv Serrano Morales, José Manuel
Vázquez Carretero, María Dolores
García Miranda, Pablo
Carvajal Vázquez, Ana Eloisa
Calonge Castrillo, María Luisa
Ilundáin Larrañeta, María Anunciación Ana
Peral Rubio, María José
author Serrano Morales, José Manuel
author_facet Serrano Morales, José Manuel
Vázquez Carretero, María Dolores
García Miranda, Pablo
Carvajal Vázquez, Ana Eloisa
Calonge Castrillo, María Luisa
Ilundáin Larrañeta, María Anunciación Ana
Peral Rubio, María José
author_role author
author2 Vázquez Carretero, María Dolores
García Miranda, Pablo
Carvajal Vázquez, Ana Eloisa
Calonge Castrillo, María Luisa
Ilundáin Larrañeta, María Anunciación Ana
Peral Rubio, María José
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Fisiología
Junta de Andalucía
dc.subject.none.fl_str_mv Akt
ApoER2
Colitis
Colon cancer
DNMT-1
p53
Reelin
topic Akt
ApoER2
Colitis
Colon cancer
DNMT-1
p53
Reelin
description Previous observations made in human and mouse colons suggest that reelin protects the colon from pathology. In this study, we evaluated reelin expression during the transition from either colitis or precancerous lesions to colon cancer and tried to elucidate reelin regulation under these transition processes. Samples of healthy and pathological colons from humans and mice treated with either azoxymethane/dextran sulfate sodium (DSS) or azoxymethane alone were used. The relative abundances of reelin, DNMT-1 and ApoER2 mRNAs were determined by PCR in the colon samples cited above and in the tissue adjacent to mouse colon polyps and adenocarcinomas. In both, humans and mice, reelin mRNA abundance increased significantly in ulcerative colitis and slightly in polyps and decreased in adenomas and adenocarcinomas. Reelin expression was higher in the tissue adjacent to the colon adenocarcinoma and lower in the lesion itself. The reelin expression changes may result, at least in part, from those in DNMT-1 and appear to be independent of ApoER2. Lack of reelin downregulated p-Akt and p53 in healthy colon and prevented their increases in the inflamed colon, whereas it increased GSK-3β in DSS-untreated mice. In conclusion, reelin mRNA abundance depends on the severity of the colon pathology, and its upregulation in response to initial injuries might prevent the beginning of colon cancer, whereas reelin repression favors it. Increased p53 expression and activation may be involved in this protection. We also propose that changes in colon reelin abundance could be used to predict colon pathology progression.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/139336
https://doi.org/10.3390/biology11101406
url https://hdl.handle.net/11441/139336
https://doi.org/10.3390/biology11101406
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Biology, 11 (10), 1406.
CTS 5884
2021/1123 BIO-144
https://doi.org/10.3390/biology11101406
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 Multidisciplinary Digital Publishing Institute (MDPI)
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute (MDPI)
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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score 15,300724

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