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Mycotoxin Deoxynivalenol Has Different Impacts on Intestinal Barrier and Stem Cells by Its Route of Exposure

The different effects of deoxynivalenol (DON) on intestinal barrier and stem cells by its route of exposure remain less known. We explored the toxic effects of DON on intestinal barrier functions and stem cells after DON microinjection (luminal exposure) or addition to a culture medium (basolateral...

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Autores principales: Hanyu, Hikaru, Yokoi, Yuki, Nakamura, Kiminori, Ayabe, Tokiyoshi, Tanaka, Keisuke, Uno, Kinuko, Miyajima, Katsuhiro, Saito, Yuki, Iwatsuki, Ken, Shimizu, Makoto, Tadaishi, Miki, Kobayashi-Hattori, Kazuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598581/
https://www.ncbi.nlm.nih.gov/pubmed/32987679
http://dx.doi.org/10.3390/toxins12100610
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author Hanyu, Hikaru
Yokoi, Yuki
Nakamura, Kiminori
Ayabe, Tokiyoshi
Tanaka, Keisuke
Uno, Kinuko
Miyajima, Katsuhiro
Saito, Yuki
Iwatsuki, Ken
Shimizu, Makoto
Tadaishi, Miki
Kobayashi-Hattori, Kazuo
author_facet Hanyu, Hikaru
Yokoi, Yuki
Nakamura, Kiminori
Ayabe, Tokiyoshi
Tanaka, Keisuke
Uno, Kinuko
Miyajima, Katsuhiro
Saito, Yuki
Iwatsuki, Ken
Shimizu, Makoto
Tadaishi, Miki
Kobayashi-Hattori, Kazuo
author_sort Hanyu, Hikaru
collection PubMed
description The different effects of deoxynivalenol (DON) on intestinal barrier and stem cells by its route of exposure remain less known. We explored the toxic effects of DON on intestinal barrier functions and stem cells after DON microinjection (luminal exposure) or addition to a culture medium (basolateral exposure) using three-dimensional mouse intestinal organoids (enteroids). The influx test using fluorescein-labeled dextran showed that basolateral DON exposure (1 micromolar (µM) disrupted intestinal barrier functions in enteroids compared with luminal DON exposure at the same concentration. Moreover, an immunofluorescence experiment of intestinal epithelial proteins, such as E-cadherin, claudin, zonula occludens-1 (ZO-1), and occludin, exhibited that only basolateral DON exposure broke down intestinal epithelial integrity. A time-lapse analysis using enteroids from leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5)-enhanced green fluorescence protein (EGFP) transgenic mice and 5-ethynyl-2-deoxyuridine (EdU) assay indicated that only the basolateral DON exposure, but not luminal DON exposure, suppressed Lgr5(+) stem cell count and proliferative cell ratio, respectively. These results revealed that basolateral DON exposure has larger impacts on intestinal barrier function and stem cells than luminal DON exposure. This is the first report that DON had different impacts on intestinal stem cells depending on the administration route. In addition, RNA sequencing analysis showed different expression of genes among enteroids after basolateral and luminal DON exposure.
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spelling pubmed-75985812020-10-31 Mycotoxin Deoxynivalenol Has Different Impacts on Intestinal Barrier and Stem Cells by Its Route of Exposure Hanyu, Hikaru Yokoi, Yuki Nakamura, Kiminori Ayabe, Tokiyoshi Tanaka, Keisuke Uno, Kinuko Miyajima, Katsuhiro Saito, Yuki Iwatsuki, Ken Shimizu, Makoto Tadaishi, Miki Kobayashi-Hattori, Kazuo Toxins (Basel) Article The different effects of deoxynivalenol (DON) on intestinal barrier and stem cells by its route of exposure remain less known. We explored the toxic effects of DON on intestinal barrier functions and stem cells after DON microinjection (luminal exposure) or addition to a culture medium (basolateral exposure) using three-dimensional mouse intestinal organoids (enteroids). The influx test using fluorescein-labeled dextran showed that basolateral DON exposure (1 micromolar (µM) disrupted intestinal barrier functions in enteroids compared with luminal DON exposure at the same concentration. Moreover, an immunofluorescence experiment of intestinal epithelial proteins, such as E-cadherin, claudin, zonula occludens-1 (ZO-1), and occludin, exhibited that only basolateral DON exposure broke down intestinal epithelial integrity. A time-lapse analysis using enteroids from leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5)-enhanced green fluorescence protein (EGFP) transgenic mice and 5-ethynyl-2-deoxyuridine (EdU) assay indicated that only the basolateral DON exposure, but not luminal DON exposure, suppressed Lgr5(+) stem cell count and proliferative cell ratio, respectively. These results revealed that basolateral DON exposure has larger impacts on intestinal barrier function and stem cells than luminal DON exposure. This is the first report that DON had different impacts on intestinal stem cells depending on the administration route. In addition, RNA sequencing analysis showed different expression of genes among enteroids after basolateral and luminal DON exposure. MDPI 2020-09-24 /pmc/articles/PMC7598581/ /pubmed/32987679 http://dx.doi.org/10.3390/toxins12100610 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hanyu, Hikaru
Yokoi, Yuki
Nakamura, Kiminori
Ayabe, Tokiyoshi
Tanaka, Keisuke
Uno, Kinuko
Miyajima, Katsuhiro
Saito, Yuki
Iwatsuki, Ken
Shimizu, Makoto
Tadaishi, Miki
Kobayashi-Hattori, Kazuo
Mycotoxin Deoxynivalenol Has Different Impacts on Intestinal Barrier and Stem Cells by Its Route of Exposure
title Mycotoxin Deoxynivalenol Has Different Impacts on Intestinal Barrier and Stem Cells by Its Route of Exposure
title_full Mycotoxin Deoxynivalenol Has Different Impacts on Intestinal Barrier and Stem Cells by Its Route of Exposure
title_fullStr Mycotoxin Deoxynivalenol Has Different Impacts on Intestinal Barrier and Stem Cells by Its Route of Exposure
title_full_unstemmed Mycotoxin Deoxynivalenol Has Different Impacts on Intestinal Barrier and Stem Cells by Its Route of Exposure
title_short Mycotoxin Deoxynivalenol Has Different Impacts on Intestinal Barrier and Stem Cells by Its Route of Exposure
title_sort mycotoxin deoxynivalenol has different impacts on intestinal barrier and stem cells by its route of exposure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598581/
https://www.ncbi.nlm.nih.gov/pubmed/32987679
http://dx.doi.org/10.3390/toxins12100610
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