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Indoxyl Sulfate as a Mediator Involved in Dysregulation of Pulmonary Aquaporin-5 in Acute Lung Injury Caused by Acute Kidney Injury

High mortality of acute kidney injury (AKI) is associated with acute lung injury (ALI), which is a typical complication of AKI. Although it is suggested that dysregulation of lung salt and water channels following AKI plays a pivotal role in ALI, the mechanism of its dysregulation has not been eluci...

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Autores principales: Yabuuchi, Nozomi, Sagata, Masataka, Saigo, Chika, Yoneda, Go, Yamamoto, Yuko, Nomura, Yui, Nishi, Kazuhiko, Fujino, Rika, Jono, Hirofumi, Saito, Hideyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297646/
https://www.ncbi.nlm.nih.gov/pubmed/28025487
http://dx.doi.org/10.3390/ijms18010011
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author Yabuuchi, Nozomi
Sagata, Masataka
Saigo, Chika
Yoneda, Go
Yamamoto, Yuko
Nomura, Yui
Nishi, Kazuhiko
Fujino, Rika
Jono, Hirofumi
Saito, Hideyuki
author_facet Yabuuchi, Nozomi
Sagata, Masataka
Saigo, Chika
Yoneda, Go
Yamamoto, Yuko
Nomura, Yui
Nishi, Kazuhiko
Fujino, Rika
Jono, Hirofumi
Saito, Hideyuki
author_sort Yabuuchi, Nozomi
collection PubMed
description High mortality of acute kidney injury (AKI) is associated with acute lung injury (ALI), which is a typical complication of AKI. Although it is suggested that dysregulation of lung salt and water channels following AKI plays a pivotal role in ALI, the mechanism of its dysregulation has not been elucidated. Here, we examined the involvement of a typical oxidative stress-inducing uremic toxin, indoxyl sulfate (IS), in the dysregulation of the pulmonary predominant water channel, aquaporin 5 (AQP-5), in bilateral nephrectomy (BNx)-induced AKI model rats. BNx evoked AKI with the increases in serum creatinine (SCr), blood urea nitrogen (BUN) and serum IS levels and exhibited thickening of interstitial tissue in the lung. Administration of AST-120, clinically-used oral spherical adsorptive carbon beads, resulted in a significant decrease in serum IS level and thickening of interstitial tissue, which was accompanied with the decreases in IS accumulation in various tissues, especially lung. Interestingly, a significant decrease in AQP-5 expression of lung was observed in BNx rats. Moreover, the BNx-induced decrease in pulmonary AQP-5 protein expression was markedly restored by oral administration of AST-120. These results suggest that BNx-induced AKI causes dysregulation of pulmonary AQP-5 expression, in which IS could play a toxico-physiological role as a mediator involved in renopulmonary crosstalk.
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spelling pubmed-52976462017-02-10 Indoxyl Sulfate as a Mediator Involved in Dysregulation of Pulmonary Aquaporin-5 in Acute Lung Injury Caused by Acute Kidney Injury Yabuuchi, Nozomi Sagata, Masataka Saigo, Chika Yoneda, Go Yamamoto, Yuko Nomura, Yui Nishi, Kazuhiko Fujino, Rika Jono, Hirofumi Saito, Hideyuki Int J Mol Sci Article High mortality of acute kidney injury (AKI) is associated with acute lung injury (ALI), which is a typical complication of AKI. Although it is suggested that dysregulation of lung salt and water channels following AKI plays a pivotal role in ALI, the mechanism of its dysregulation has not been elucidated. Here, we examined the involvement of a typical oxidative stress-inducing uremic toxin, indoxyl sulfate (IS), in the dysregulation of the pulmonary predominant water channel, aquaporin 5 (AQP-5), in bilateral nephrectomy (BNx)-induced AKI model rats. BNx evoked AKI with the increases in serum creatinine (SCr), blood urea nitrogen (BUN) and serum IS levels and exhibited thickening of interstitial tissue in the lung. Administration of AST-120, clinically-used oral spherical adsorptive carbon beads, resulted in a significant decrease in serum IS level and thickening of interstitial tissue, which was accompanied with the decreases in IS accumulation in various tissues, especially lung. Interestingly, a significant decrease in AQP-5 expression of lung was observed in BNx rats. Moreover, the BNx-induced decrease in pulmonary AQP-5 protein expression was markedly restored by oral administration of AST-120. These results suggest that BNx-induced AKI causes dysregulation of pulmonary AQP-5 expression, in which IS could play a toxico-physiological role as a mediator involved in renopulmonary crosstalk. MDPI 2016-12-23 /pmc/articles/PMC5297646/ /pubmed/28025487 http://dx.doi.org/10.3390/ijms18010011 Text en © 2016 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
Yabuuchi, Nozomi
Sagata, Masataka
Saigo, Chika
Yoneda, Go
Yamamoto, Yuko
Nomura, Yui
Nishi, Kazuhiko
Fujino, Rika
Jono, Hirofumi
Saito, Hideyuki
Indoxyl Sulfate as a Mediator Involved in Dysregulation of Pulmonary Aquaporin-5 in Acute Lung Injury Caused by Acute Kidney Injury
title Indoxyl Sulfate as a Mediator Involved in Dysregulation of Pulmonary Aquaporin-5 in Acute Lung Injury Caused by Acute Kidney Injury
title_full Indoxyl Sulfate as a Mediator Involved in Dysregulation of Pulmonary Aquaporin-5 in Acute Lung Injury Caused by Acute Kidney Injury
title_fullStr Indoxyl Sulfate as a Mediator Involved in Dysregulation of Pulmonary Aquaporin-5 in Acute Lung Injury Caused by Acute Kidney Injury
title_full_unstemmed Indoxyl Sulfate as a Mediator Involved in Dysregulation of Pulmonary Aquaporin-5 in Acute Lung Injury Caused by Acute Kidney Injury
title_short Indoxyl Sulfate as a Mediator Involved in Dysregulation of Pulmonary Aquaporin-5 in Acute Lung Injury Caused by Acute Kidney Injury
title_sort indoxyl sulfate as a mediator involved in dysregulation of pulmonary aquaporin-5 in acute lung injury caused by acute kidney injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297646/
https://www.ncbi.nlm.nih.gov/pubmed/28025487
http://dx.doi.org/10.3390/ijms18010011
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