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Selenium and the 15kDa Selenoprotein Impact Colorectal Tumorigenesis by Modulating Intestinal Barrier Integrity

Selenoproteins play important roles in many cellular functions and biochemical pathways in mammals. Our previous study showed that the deficiency of the 15 kDa selenoprotein (Selenof) significantly reduced the formation of aberrant crypt foci (ACF) in a mouse model of azoxymethane (AOM)-induced colo...

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Autores principales: Canter, Jessica A., Ernst, Sarah E., Peters, Kristin M., Carlson, Bradley A., Thielman, Noelle R. J., Grysczyk, Lara, Udofe, Precious, Yu, Yunkai, Cao, Liang, Davis, Cindy D., Gladyshev, Vadim N., Hatfield, Dolph L., Tsuji, Petra A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508755/
https://www.ncbi.nlm.nih.gov/pubmed/34638991
http://dx.doi.org/10.3390/ijms221910651
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author Canter, Jessica A.
Ernst, Sarah E.
Peters, Kristin M.
Carlson, Bradley A.
Thielman, Noelle R. J.
Grysczyk, Lara
Udofe, Precious
Yu, Yunkai
Cao, Liang
Davis, Cindy D.
Gladyshev, Vadim N.
Hatfield, Dolph L.
Tsuji, Petra A.
author_facet Canter, Jessica A.
Ernst, Sarah E.
Peters, Kristin M.
Carlson, Bradley A.
Thielman, Noelle R. J.
Grysczyk, Lara
Udofe, Precious
Yu, Yunkai
Cao, Liang
Davis, Cindy D.
Gladyshev, Vadim N.
Hatfield, Dolph L.
Tsuji, Petra A.
author_sort Canter, Jessica A.
collection PubMed
description Selenoproteins play important roles in many cellular functions and biochemical pathways in mammals. Our previous study showed that the deficiency of the 15 kDa selenoprotein (Selenof) significantly reduced the formation of aberrant crypt foci (ACF) in a mouse model of azoxymethane (AOM)-induced colon carcinogenesis. The objective of this study was to examine the effects of Selenof on inflammatory tumorigenesis, and whether dietary selenium modified these effects. For 20 weeks post-weaning, Selenof-knockout (KO) mice and littermate controls were fed diets that were either deficient, adequate or high in sodium selenite. Colon tumors were induced with AOM and dextran sulfate sodium. Surprisingly, KO mice had drastically fewer ACF but developed a similar number of tumors as their littermate controls. Expression of genes important in inflammatory colorectal cancer and those relevant to epithelial barrier function was assessed, in addition to structural differences via tissue histology. Our findings point to Selenof’s potential role in intestinal barrier integrity and structural changes in glandular and mucin-producing goblet cells in the mucosa and submucosa, which may determine the type of tumor developing.
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spelling pubmed-85087552021-10-13 Selenium and the 15kDa Selenoprotein Impact Colorectal Tumorigenesis by Modulating Intestinal Barrier Integrity Canter, Jessica A. Ernst, Sarah E. Peters, Kristin M. Carlson, Bradley A. Thielman, Noelle R. J. Grysczyk, Lara Udofe, Precious Yu, Yunkai Cao, Liang Davis, Cindy D. Gladyshev, Vadim N. Hatfield, Dolph L. Tsuji, Petra A. Int J Mol Sci Article Selenoproteins play important roles in many cellular functions and biochemical pathways in mammals. Our previous study showed that the deficiency of the 15 kDa selenoprotein (Selenof) significantly reduced the formation of aberrant crypt foci (ACF) in a mouse model of azoxymethane (AOM)-induced colon carcinogenesis. The objective of this study was to examine the effects of Selenof on inflammatory tumorigenesis, and whether dietary selenium modified these effects. For 20 weeks post-weaning, Selenof-knockout (KO) mice and littermate controls were fed diets that were either deficient, adequate or high in sodium selenite. Colon tumors were induced with AOM and dextran sulfate sodium. Surprisingly, KO mice had drastically fewer ACF but developed a similar number of tumors as their littermate controls. Expression of genes important in inflammatory colorectal cancer and those relevant to epithelial barrier function was assessed, in addition to structural differences via tissue histology. Our findings point to Selenof’s potential role in intestinal barrier integrity and structural changes in glandular and mucin-producing goblet cells in the mucosa and submucosa, which may determine the type of tumor developing. MDPI 2021-09-30 /pmc/articles/PMC8508755/ /pubmed/34638991 http://dx.doi.org/10.3390/ijms221910651 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Canter, Jessica A.
Ernst, Sarah E.
Peters, Kristin M.
Carlson, Bradley A.
Thielman, Noelle R. J.
Grysczyk, Lara
Udofe, Precious
Yu, Yunkai
Cao, Liang
Davis, Cindy D.
Gladyshev, Vadim N.
Hatfield, Dolph L.
Tsuji, Petra A.
Selenium and the 15kDa Selenoprotein Impact Colorectal Tumorigenesis by Modulating Intestinal Barrier Integrity
title Selenium and the 15kDa Selenoprotein Impact Colorectal Tumorigenesis by Modulating Intestinal Barrier Integrity
title_full Selenium and the 15kDa Selenoprotein Impact Colorectal Tumorigenesis by Modulating Intestinal Barrier Integrity
title_fullStr Selenium and the 15kDa Selenoprotein Impact Colorectal Tumorigenesis by Modulating Intestinal Barrier Integrity
title_full_unstemmed Selenium and the 15kDa Selenoprotein Impact Colorectal Tumorigenesis by Modulating Intestinal Barrier Integrity
title_short Selenium and the 15kDa Selenoprotein Impact Colorectal Tumorigenesis by Modulating Intestinal Barrier Integrity
title_sort selenium and the 15kda selenoprotein impact colorectal tumorigenesis by modulating intestinal barrier integrity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508755/
https://www.ncbi.nlm.nih.gov/pubmed/34638991
http://dx.doi.org/10.3390/ijms221910651
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