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Dioxin Receptor Adjusts Liver Regeneration After Acute Toxic Injury and Protects Against Liver Carcinogenesis

The aryl hydrocarbon receptor (AhR) has roles in cell proliferation, differentiation and organ homeostasis, including the liver. AhR depletion induces undifferentiation and pluripotency in normal and transformed cells. Here, AhR-null mice (AhR−/−) were used to explore whether AhR controls liver rege...

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Autores principales: Moreno-Marín, Nuria, Barrasa, Eva, Morales-Hernández, Antonio, Paniagua, Beroé, Blanco-Fernández, Gerardo, Merino, Jaime M., Fernández-Salguero, Pedro M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585208/
https://www.ncbi.nlm.nih.gov/pubmed/28874739
http://dx.doi.org/10.1038/s41598-017-10984-w
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author Moreno-Marín, Nuria
Barrasa, Eva
Morales-Hernández, Antonio
Paniagua, Beroé
Blanco-Fernández, Gerardo
Merino, Jaime M.
Fernández-Salguero, Pedro M.
author_facet Moreno-Marín, Nuria
Barrasa, Eva
Morales-Hernández, Antonio
Paniagua, Beroé
Blanco-Fernández, Gerardo
Merino, Jaime M.
Fernández-Salguero, Pedro M.
author_sort Moreno-Marín, Nuria
collection PubMed
description The aryl hydrocarbon receptor (AhR) has roles in cell proliferation, differentiation and organ homeostasis, including the liver. AhR depletion induces undifferentiation and pluripotency in normal and transformed cells. Here, AhR-null mice (AhR−/−) were used to explore whether AhR controls liver regeneration and carcinogenesis by restricting the expansion of stem-like cells and the expression of pluripotency genes. Short-term CCl(4) liver damage was earlier and more efficiently repaired in AhR−/− than in AhR+/+ mice. Stem-like CK14 + and TBX3 + and pluripotency-expressing OCT4 + and NANOG + cells expanded sooner in AhR−/− than in AhR+/+ regenerating livers. Stem-like side population cells (SP) isolated from AhR−/− livers had increased β-catenin (β-Cat) signaling with overexpression of Axin2, Dkk1 and Cyclin D1. Interestingly, β-Cat, Axin2 and Dkk1 also increased during regeneration but more notably in AhR-null livers. Liver carcinogenesis induced by diethylnitrosamine (DEN) produced large carcinomas in all AhR−/− mice but mostly premalignant adenomas in less than half of AhR+/+ mice. AhR-null tumoral tissue, but not their surrounding non-tumoral parenchyma, had nuclear β-Cat and Axin2 overexpression. OCT4 and NANOG were nevertheless similarly expressed in AhR+/+ and AhR−/− lesions. We suggest that AhR may serve to adjust liver repair and to block tumorigenesis by modulating stem-like cells and β-Cat signaling.
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spelling pubmed-55852082017-09-06 Dioxin Receptor Adjusts Liver Regeneration After Acute Toxic Injury and Protects Against Liver Carcinogenesis Moreno-Marín, Nuria Barrasa, Eva Morales-Hernández, Antonio Paniagua, Beroé Blanco-Fernández, Gerardo Merino, Jaime M. Fernández-Salguero, Pedro M. Sci Rep Article The aryl hydrocarbon receptor (AhR) has roles in cell proliferation, differentiation and organ homeostasis, including the liver. AhR depletion induces undifferentiation and pluripotency in normal and transformed cells. Here, AhR-null mice (AhR−/−) were used to explore whether AhR controls liver regeneration and carcinogenesis by restricting the expansion of stem-like cells and the expression of pluripotency genes. Short-term CCl(4) liver damage was earlier and more efficiently repaired in AhR−/− than in AhR+/+ mice. Stem-like CK14 + and TBX3 + and pluripotency-expressing OCT4 + and NANOG + cells expanded sooner in AhR−/− than in AhR+/+ regenerating livers. Stem-like side population cells (SP) isolated from AhR−/− livers had increased β-catenin (β-Cat) signaling with overexpression of Axin2, Dkk1 and Cyclin D1. Interestingly, β-Cat, Axin2 and Dkk1 also increased during regeneration but more notably in AhR-null livers. Liver carcinogenesis induced by diethylnitrosamine (DEN) produced large carcinomas in all AhR−/− mice but mostly premalignant adenomas in less than half of AhR+/+ mice. AhR-null tumoral tissue, but not their surrounding non-tumoral parenchyma, had nuclear β-Cat and Axin2 overexpression. OCT4 and NANOG were nevertheless similarly expressed in AhR+/+ and AhR−/− lesions. We suggest that AhR may serve to adjust liver repair and to block tumorigenesis by modulating stem-like cells and β-Cat signaling. Nature Publishing Group UK 2017-09-05 /pmc/articles/PMC5585208/ /pubmed/28874739 http://dx.doi.org/10.1038/s41598-017-10984-w Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Moreno-Marín, Nuria
Barrasa, Eva
Morales-Hernández, Antonio
Paniagua, Beroé
Blanco-Fernández, Gerardo
Merino, Jaime M.
Fernández-Salguero, Pedro M.
Dioxin Receptor Adjusts Liver Regeneration After Acute Toxic Injury and Protects Against Liver Carcinogenesis
title Dioxin Receptor Adjusts Liver Regeneration After Acute Toxic Injury and Protects Against Liver Carcinogenesis
title_full Dioxin Receptor Adjusts Liver Regeneration After Acute Toxic Injury and Protects Against Liver Carcinogenesis
title_fullStr Dioxin Receptor Adjusts Liver Regeneration After Acute Toxic Injury and Protects Against Liver Carcinogenesis
title_full_unstemmed Dioxin Receptor Adjusts Liver Regeneration After Acute Toxic Injury and Protects Against Liver Carcinogenesis
title_short Dioxin Receptor Adjusts Liver Regeneration After Acute Toxic Injury and Protects Against Liver Carcinogenesis
title_sort dioxin receptor adjusts liver regeneration after acute toxic injury and protects against liver carcinogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585208/
https://www.ncbi.nlm.nih.gov/pubmed/28874739
http://dx.doi.org/10.1038/s41598-017-10984-w
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