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Upregulation of Claudin-7 Expression by Angiotensin II in Colonic Epithelial Cells of Mice Fed with NaCl-Depleted Diets

Dietary NaCl depletion increases Na(+) and Cl(−) absorption in the colon, but the mechanisms are not fully understood. So far, we reported that the expression of claudin-7 (CLDN7), a tight junction (TJ) protein, was upregulated in the mice fed with NaCl-depleted diets, but the regulatory mechanism h...

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Autores principales: Takashina, Yui, Ishizuka, Noriko, Ikumi, Naotaka, Hayashi, Hisayoshi, Manabe, Aya, Hirota, Chieko, Tabuchi, Yoshiaki, Matsunaga, Toshiyuki, Ikari, Akira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073026/
https://www.ncbi.nlm.nih.gov/pubmed/32093310
http://dx.doi.org/10.3390/ijms21041442
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author Takashina, Yui
Ishizuka, Noriko
Ikumi, Naotaka
Hayashi, Hisayoshi
Manabe, Aya
Hirota, Chieko
Tabuchi, Yoshiaki
Matsunaga, Toshiyuki
Ikari, Akira
author_facet Takashina, Yui
Ishizuka, Noriko
Ikumi, Naotaka
Hayashi, Hisayoshi
Manabe, Aya
Hirota, Chieko
Tabuchi, Yoshiaki
Matsunaga, Toshiyuki
Ikari, Akira
author_sort Takashina, Yui
collection PubMed
description Dietary NaCl depletion increases Na(+) and Cl(−) absorption in the colon, but the mechanisms are not fully understood. So far, we reported that the expression of claudin-7 (CLDN7), a tight junction (TJ) protein, was upregulated in the mice fed with NaCl-depleted diets, but the regulatory mechanism has not been clarified. Here, we found that angiotensin II (ANGII) increases the mRNA level of CLDN7, which was inhibited by losartan, a type 1 ANGII (AT1) receptor antagonist. Immunofluorescence measurement showed that CLDN7 is colocalized with zonula occludens-1 at the TJ in untreated and ANGII-treated cells. ANGII decreased transepithelial electrical resistance (TER) and increased permeability to C1(−) without affecting permeability to lucifer yellow, a paracellular flux marker. In contrast, TER was increased by CLDN7 knockdown in the absence and presence of ANGII. ANGII increased the nuclear distribution of phosphorylated p65 subunit of NF-κB, which was inhibited by losartan. The ANGII-induced elevation of CLDN7 expression was blocked by BAY 11-7082 (BAY), an NF-κB inhibitor. Luciferase reporter assay showed that ANGII increases promoter activity of CLDN7, which was inhibited by the treatment with losartan or BAY, and introduction of mutations in κB-binding motifs in the promoter. The binding of p65 on the promoter region of CLDN7 was increased by ANGII, which was inhibited by losartan and BAY in chromatin immunoprecipitation assay. Our data suggest that ANGII acts on AT1 receptor and increases paracellular permeability to Cl(−) mediated by the elevation of CLDN7 expression in the colon.
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spelling pubmed-70730262020-03-19 Upregulation of Claudin-7 Expression by Angiotensin II in Colonic Epithelial Cells of Mice Fed with NaCl-Depleted Diets Takashina, Yui Ishizuka, Noriko Ikumi, Naotaka Hayashi, Hisayoshi Manabe, Aya Hirota, Chieko Tabuchi, Yoshiaki Matsunaga, Toshiyuki Ikari, Akira Int J Mol Sci Article Dietary NaCl depletion increases Na(+) and Cl(−) absorption in the colon, but the mechanisms are not fully understood. So far, we reported that the expression of claudin-7 (CLDN7), a tight junction (TJ) protein, was upregulated in the mice fed with NaCl-depleted diets, but the regulatory mechanism has not been clarified. Here, we found that angiotensin II (ANGII) increases the mRNA level of CLDN7, which was inhibited by losartan, a type 1 ANGII (AT1) receptor antagonist. Immunofluorescence measurement showed that CLDN7 is colocalized with zonula occludens-1 at the TJ in untreated and ANGII-treated cells. ANGII decreased transepithelial electrical resistance (TER) and increased permeability to C1(−) without affecting permeability to lucifer yellow, a paracellular flux marker. In contrast, TER was increased by CLDN7 knockdown in the absence and presence of ANGII. ANGII increased the nuclear distribution of phosphorylated p65 subunit of NF-κB, which was inhibited by losartan. The ANGII-induced elevation of CLDN7 expression was blocked by BAY 11-7082 (BAY), an NF-κB inhibitor. Luciferase reporter assay showed that ANGII increases promoter activity of CLDN7, which was inhibited by the treatment with losartan or BAY, and introduction of mutations in κB-binding motifs in the promoter. The binding of p65 on the promoter region of CLDN7 was increased by ANGII, which was inhibited by losartan and BAY in chromatin immunoprecipitation assay. Our data suggest that ANGII acts on AT1 receptor and increases paracellular permeability to Cl(−) mediated by the elevation of CLDN7 expression in the colon. MDPI 2020-02-20 /pmc/articles/PMC7073026/ /pubmed/32093310 http://dx.doi.org/10.3390/ijms21041442 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
Takashina, Yui
Ishizuka, Noriko
Ikumi, Naotaka
Hayashi, Hisayoshi
Manabe, Aya
Hirota, Chieko
Tabuchi, Yoshiaki
Matsunaga, Toshiyuki
Ikari, Akira
Upregulation of Claudin-7 Expression by Angiotensin II in Colonic Epithelial Cells of Mice Fed with NaCl-Depleted Diets
title Upregulation of Claudin-7 Expression by Angiotensin II in Colonic Epithelial Cells of Mice Fed with NaCl-Depleted Diets
title_full Upregulation of Claudin-7 Expression by Angiotensin II in Colonic Epithelial Cells of Mice Fed with NaCl-Depleted Diets
title_fullStr Upregulation of Claudin-7 Expression by Angiotensin II in Colonic Epithelial Cells of Mice Fed with NaCl-Depleted Diets
title_full_unstemmed Upregulation of Claudin-7 Expression by Angiotensin II in Colonic Epithelial Cells of Mice Fed with NaCl-Depleted Diets
title_short Upregulation of Claudin-7 Expression by Angiotensin II in Colonic Epithelial Cells of Mice Fed with NaCl-Depleted Diets
title_sort upregulation of claudin-7 expression by angiotensin ii in colonic epithelial cells of mice fed with nacl-depleted diets
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073026/
https://www.ncbi.nlm.nih.gov/pubmed/32093310
http://dx.doi.org/10.3390/ijms21041442
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