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Up-regulation of claudin-2 expression by aldosterone in colonic epithelial cells of mice fed with NaCl-depleted diets

Dietary NaCl depletion increases Na(+) absorption and K(+) secretion in the colon, but the mechanisms are not fully understood. In mice fed with NaCl-depleted diets, the expression of claudin-2 and -7 increased compared to those in control mice. Aldosterone (ALD) concentration was also increased. We...

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Autores principales: Furukawa, Chisa, Ishizuka, Noriko, Hayashi, Hisayoshi, Fujii, Naoko, Manabe, Aya, Tabuchi, Yoshiaki, Matsunaga, Toshiyuki, Endo, Satoshi, Ikari, Akira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610316/
https://www.ncbi.nlm.nih.gov/pubmed/28939904
http://dx.doi.org/10.1038/s41598-017-12494-1
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author Furukawa, Chisa
Ishizuka, Noriko
Hayashi, Hisayoshi
Fujii, Naoko
Manabe, Aya
Tabuchi, Yoshiaki
Matsunaga, Toshiyuki
Endo, Satoshi
Ikari, Akira
author_facet Furukawa, Chisa
Ishizuka, Noriko
Hayashi, Hisayoshi
Fujii, Naoko
Manabe, Aya
Tabuchi, Yoshiaki
Matsunaga, Toshiyuki
Endo, Satoshi
Ikari, Akira
author_sort Furukawa, Chisa
collection PubMed
description Dietary NaCl depletion increases Na(+) absorption and K(+) secretion in the colon, but the mechanisms are not fully understood. In mice fed with NaCl-depleted diets, the expression of claudin-2 and -7 increased compared to those in control mice. Aldosterone (ALD) concentration was also increased. We examined the regulatory mechanism of claudin expression by ALD using the murine colonic epithelial MCE301 cells. ALD dose-dependently increased claudin-2 expression without affecting the expression of claudin-4, -7, -8, and -15. ALD increased nuclear distribution of mineralocorticoid receptor (MR), which was inhibited by spironolactone, an MR antagonist. The ALD-induced elevation of claudin-2 mRNA and protein expression was inhibited by spironolactone, but not by RU-486, a glucocorticoid receptor antagonist. Luciferase reporter assay showed that ALD interacts with the promoter region between -2,021 and -2,008 of human claudin-2. The binding of MR on the promoter region of claudin-2 was increased by ALD, which was inhibited by spironolactone in chromatin immunoprecipitation assay. Our data suggest that ALD acts on MR and increases paracellular permeability to ions mediated by the elevation of claudin-2 expression in the colon. NaCl depletion may increase ALD secretion from adrenal cortex, resulting in the elevation of paracellular permeability to cations in the colon.
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spelling pubmed-56103162017-10-10 Up-regulation of claudin-2 expression by aldosterone in colonic epithelial cells of mice fed with NaCl-depleted diets Furukawa, Chisa Ishizuka, Noriko Hayashi, Hisayoshi Fujii, Naoko Manabe, Aya Tabuchi, Yoshiaki Matsunaga, Toshiyuki Endo, Satoshi Ikari, Akira Sci Rep Article Dietary NaCl depletion increases Na(+) absorption and K(+) secretion in the colon, but the mechanisms are not fully understood. In mice fed with NaCl-depleted diets, the expression of claudin-2 and -7 increased compared to those in control mice. Aldosterone (ALD) concentration was also increased. We examined the regulatory mechanism of claudin expression by ALD using the murine colonic epithelial MCE301 cells. ALD dose-dependently increased claudin-2 expression without affecting the expression of claudin-4, -7, -8, and -15. ALD increased nuclear distribution of mineralocorticoid receptor (MR), which was inhibited by spironolactone, an MR antagonist. The ALD-induced elevation of claudin-2 mRNA and protein expression was inhibited by spironolactone, but not by RU-486, a glucocorticoid receptor antagonist. Luciferase reporter assay showed that ALD interacts with the promoter region between -2,021 and -2,008 of human claudin-2. The binding of MR on the promoter region of claudin-2 was increased by ALD, which was inhibited by spironolactone in chromatin immunoprecipitation assay. Our data suggest that ALD acts on MR and increases paracellular permeability to ions mediated by the elevation of claudin-2 expression in the colon. NaCl depletion may increase ALD secretion from adrenal cortex, resulting in the elevation of paracellular permeability to cations in the colon. Nature Publishing Group UK 2017-09-22 /pmc/articles/PMC5610316/ /pubmed/28939904 http://dx.doi.org/10.1038/s41598-017-12494-1 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
Furukawa, Chisa
Ishizuka, Noriko
Hayashi, Hisayoshi
Fujii, Naoko
Manabe, Aya
Tabuchi, Yoshiaki
Matsunaga, Toshiyuki
Endo, Satoshi
Ikari, Akira
Up-regulation of claudin-2 expression by aldosterone in colonic epithelial cells of mice fed with NaCl-depleted diets
title Up-regulation of claudin-2 expression by aldosterone in colonic epithelial cells of mice fed with NaCl-depleted diets
title_full Up-regulation of claudin-2 expression by aldosterone in colonic epithelial cells of mice fed with NaCl-depleted diets
title_fullStr Up-regulation of claudin-2 expression by aldosterone in colonic epithelial cells of mice fed with NaCl-depleted diets
title_full_unstemmed Up-regulation of claudin-2 expression by aldosterone in colonic epithelial cells of mice fed with NaCl-depleted diets
title_short Up-regulation of claudin-2 expression by aldosterone in colonic epithelial cells of mice fed with NaCl-depleted diets
title_sort up-regulation of claudin-2 expression by aldosterone in colonic epithelial cells of mice fed with nacl-depleted diets
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610316/
https://www.ncbi.nlm.nih.gov/pubmed/28939904
http://dx.doi.org/10.1038/s41598-017-12494-1
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