Reelin protects from colon pathology by maintaining the intestinal barrier integrity and repressing tumorigenic genes
We previously reported that reelin, an extracellular matrix protein first known for its key role in neuronal migration, reduces the susceptibility to dextran sulphate sodium (DSS)-colitis. The aim of the current study was to determine whether reelin protects from colorectal cancer and how reelin def...
| Autores: | , , , , , , |
|---|---|
| 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:11441/85335 |
| Acceso en línea: | https://hdl.handle.net/11441/85335 https://doi.org/10.1016/j.bbadis.2017.05.026 |
| Access Level: | acceso abierto |
| Palabra clave: | Cancer Colitis Reelin |
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Reelin protects from colon pathology by maintaining the intestinal barrier integrity and repressing tumorigenic genesCarvajal Vázquez, Ana EloisaSerrano Morales, José ManuelVázquez Carretero, María DoloresGarcía Miranda, PabloCalonge Castrillo, María LuisaPeral Rubio, María JoséIlundáin Larrañeta, María Anunciación AnaCancerColitisReelinWe previously reported that reelin, an extracellular matrix protein first known for its key role in neuronal migration, reduces the susceptibility to dextran sulphate sodium (DSS)-colitis. The aim of the current study was to determine whether reelin protects from colorectal cancer and how reelin defends from colon pathology. In the colon of wild-type and of mice lacking reelin (reeler mice) we have analysed the: i) epithelium cell renewal processes, ii) morphology, iii) Sox9, Cdx2, Smad5, Cyclin D1, IL-6 and IFNγ mRNA abundance in DSS-treated and untreated mice, and iv) development of azoxymethane/DSS-induced colorectal cancer, using histological and real time-PCR methodologies. The reeler mutation increases colitis-associated tumorigenesis, with increased tumours number and size. It also impairs the intestinal barrier because it reduces cell proliferation, migration, differentiation and apoptosis; decreases the number and maturation of goblet cells, and expands the intercellular space of the desmosomes. The intestinal barrier impairment might explain the increased susceptibility to colon pathology exhibited by the reeler mice and is at least mediated by the down-regulation of Sox9 and Cdx2. In response to DSS-colitis, the reeler colon increases the mRNA abundance of IL-6, Smad5 and Cyclin D1 and decreases that of IFNγ, conditions that might result in the increased colitis-associated tumorigenesis found in the reeler mice. In conclusion, the results highlight a role for reelin in maintaining intestinal epithelial cell homeostasis and providing resistance against colon pathology.España, Junta de Andalucía CTS 5884ElsevierFisiología2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/85335https://doi.org/10.1016/j.bbadis.2017.05.026reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésBiochimica et Biophysica Acta Molecular and Cell Biology of Lipids, 1863 (9), 2126-2134.CTS 5884http://dx.doi.org/10.1016/j.bbadis.2017.05.026info:eu-repo/semantics/openAccessoai:idus.us.es:11441/853352026-06-17T12:51:07Z |
| dc.title.none.fl_str_mv |
Reelin protects from colon pathology by maintaining the intestinal barrier integrity and repressing tumorigenic genes |
| title |
Reelin protects from colon pathology by maintaining the intestinal barrier integrity and repressing tumorigenic genes |
| spellingShingle |
Reelin protects from colon pathology by maintaining the intestinal barrier integrity and repressing tumorigenic genes Carvajal Vázquez, Ana Eloisa Cancer Colitis Reelin |
| title_short |
Reelin protects from colon pathology by maintaining the intestinal barrier integrity and repressing tumorigenic genes |
| title_full |
Reelin protects from colon pathology by maintaining the intestinal barrier integrity and repressing tumorigenic genes |
| title_fullStr |
Reelin protects from colon pathology by maintaining the intestinal barrier integrity and repressing tumorigenic genes |
| title_full_unstemmed |
Reelin protects from colon pathology by maintaining the intestinal barrier integrity and repressing tumorigenic genes |
| title_sort |
Reelin protects from colon pathology by maintaining the intestinal barrier integrity and repressing tumorigenic genes |
| dc.creator.none.fl_str_mv |
Carvajal Vázquez, Ana Eloisa Serrano Morales, José Manuel Vázquez Carretero, María Dolores García Miranda, Pablo Calonge Castrillo, María Luisa Peral Rubio, María José Ilundáin Larrañeta, María Anunciación Ana |
| author |
Carvajal Vázquez, Ana Eloisa |
| author_facet |
Carvajal Vázquez, Ana Eloisa Serrano Morales, José Manuel Vázquez Carretero, María Dolores García Miranda, Pablo Calonge Castrillo, María Luisa Peral Rubio, María José Ilundáin Larrañeta, María Anunciación Ana |
| author_role |
author |
| author2 |
Serrano Morales, José Manuel Vázquez Carretero, María Dolores García Miranda, Pablo Calonge Castrillo, María Luisa Peral Rubio, María José Ilundáin Larrañeta, María Anunciación Ana |
| author2_role |
author author author author author author |
| dc.contributor.none.fl_str_mv |
Fisiología |
| dc.subject.none.fl_str_mv |
Cancer Colitis Reelin |
| topic |
Cancer Colitis Reelin |
| description |
We previously reported that reelin, an extracellular matrix protein first known for its key role in neuronal migration, reduces the susceptibility to dextran sulphate sodium (DSS)-colitis. The aim of the current study was to determine whether reelin protects from colorectal cancer and how reelin defends from colon pathology. In the colon of wild-type and of mice lacking reelin (reeler mice) we have analysed the: i) epithelium cell renewal processes, ii) morphology, iii) Sox9, Cdx2, Smad5, Cyclin D1, IL-6 and IFNγ mRNA abundance in DSS-treated and untreated mice, and iv) development of azoxymethane/DSS-induced colorectal cancer, using histological and real time-PCR methodologies. The reeler mutation increases colitis-associated tumorigenesis, with increased tumours number and size. It also impairs the intestinal barrier because it reduces cell proliferation, migration, differentiation and apoptosis; decreases the number and maturation of goblet cells, and expands the intercellular space of the desmosomes. The intestinal barrier impairment might explain the increased susceptibility to colon pathology exhibited by the reeler mice and is at least mediated by the down-regulation of Sox9 and Cdx2. In response to DSS-colitis, the reeler colon increases the mRNA abundance of IL-6, Smad5 and Cyclin D1 and decreases that of IFNγ, conditions that might result in the increased colitis-associated tumorigenesis found in the reeler mice. In conclusion, the results highlight a role for reelin in maintaining intestinal epithelial cell homeostasis and providing resistance against colon pathology. |
| 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/11441/85335 https://doi.org/10.1016/j.bbadis.2017.05.026 |
| url |
https://hdl.handle.net/11441/85335 https://doi.org/10.1016/j.bbadis.2017.05.026 |
| 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 (9), 2126-2134. CTS 5884 http://dx.doi.org/10.1016/j.bbadis.2017.05.026 |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf application/pdf |
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Elsevier |
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Elsevier |
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reponame:idUS. Depósito de Investigación de la Universidad de Sevilla instname:Universidad de Sevilla (US) |
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Universidad de Sevilla (US) |
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idUS. Depósito de Investigación de la Universidad de Sevilla |
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idUS. Depósito de Investigación de la Universidad de Sevilla |
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15,81155 |