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Morphine Induces Albuminuria by Compromising Podocyte Integrity

Morphine has been reported to accelerate the progression of chronic kidney disease. However, whether morphine affects slit diaphragm (SD), the major constituent of glomerular filtration barrier, is still unclear. In the present study, we examined the effect of morphine on glomerular filtration barri...

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Autores principales: Lan, Xiqian, Rai, Partab, Chandel, Nirupama, Cheng, Kang, Lederman, Rivka, Saleem, Moin A., Mathieson, Peter W., Husain, Mohammad, Crosson, John T., Gupta, Kalpna, Malhotra, Ashwani, Singhal, Pravin C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612045/
https://www.ncbi.nlm.nih.gov/pubmed/23555556
http://dx.doi.org/10.1371/journal.pone.0055748
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author Lan, Xiqian
Rai, Partab
Chandel, Nirupama
Cheng, Kang
Lederman, Rivka
Saleem, Moin A.
Mathieson, Peter W.
Husain, Mohammad
Crosson, John T.
Gupta, Kalpna
Malhotra, Ashwani
Singhal, Pravin C.
author_facet Lan, Xiqian
Rai, Partab
Chandel, Nirupama
Cheng, Kang
Lederman, Rivka
Saleem, Moin A.
Mathieson, Peter W.
Husain, Mohammad
Crosson, John T.
Gupta, Kalpna
Malhotra, Ashwani
Singhal, Pravin C.
author_sort Lan, Xiqian
collection PubMed
description Morphine has been reported to accelerate the progression of chronic kidney disease. However, whether morphine affects slit diaphragm (SD), the major constituent of glomerular filtration barrier, is still unclear. In the present study, we examined the effect of morphine on glomerular filtration barrier in general and podocyte integrity in particular. Mice were administered either normal saline or morphine for 72 h, then urine samples were collected and kidneys were subsequently isolated for immunohistochemical studies and Western blot. For in vitro studies, human podocytes were treated with morphine and then probed for the molecular markers of slit diaphragm. Morphine-receiving mice displayed a significant increase in albuminuria and showed effacement of podocyte foot processes. In both in vivo and in vitro studies, the expression of synaptopodin, a molecular marker for podocyte integrity, and the slit diaphragm constituting molecules (SDCM), such as nephrin, podocin, and CD2-associated protein (CD2AP), were decreased in morphine-treated podocytes. In vitro studies indicated that morphine modulated podocyte expression of SDCM through opiate mu (MOR) and kappa (KOR) receptors. Since morphine also enhanced podocyte oxidative stress, the latter seems to contribute to decreased SDCM expression. In addition, AKT, p38, and JNK pathways were involved in morphine-induced down regulation of SDCM in human podocytes. These findings demonstrate that morphine has the potential to alter the glomerular filtration barrier by compromising the integrity of podocytes.
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spelling pubmed-36120452013-04-03 Morphine Induces Albuminuria by Compromising Podocyte Integrity Lan, Xiqian Rai, Partab Chandel, Nirupama Cheng, Kang Lederman, Rivka Saleem, Moin A. Mathieson, Peter W. Husain, Mohammad Crosson, John T. Gupta, Kalpna Malhotra, Ashwani Singhal, Pravin C. PLoS One Research Article Morphine has been reported to accelerate the progression of chronic kidney disease. However, whether morphine affects slit diaphragm (SD), the major constituent of glomerular filtration barrier, is still unclear. In the present study, we examined the effect of morphine on glomerular filtration barrier in general and podocyte integrity in particular. Mice were administered either normal saline or morphine for 72 h, then urine samples were collected and kidneys were subsequently isolated for immunohistochemical studies and Western blot. For in vitro studies, human podocytes were treated with morphine and then probed for the molecular markers of slit diaphragm. Morphine-receiving mice displayed a significant increase in albuminuria and showed effacement of podocyte foot processes. In both in vivo and in vitro studies, the expression of synaptopodin, a molecular marker for podocyte integrity, and the slit diaphragm constituting molecules (SDCM), such as nephrin, podocin, and CD2-associated protein (CD2AP), were decreased in morphine-treated podocytes. In vitro studies indicated that morphine modulated podocyte expression of SDCM through opiate mu (MOR) and kappa (KOR) receptors. Since morphine also enhanced podocyte oxidative stress, the latter seems to contribute to decreased SDCM expression. In addition, AKT, p38, and JNK pathways were involved in morphine-induced down regulation of SDCM in human podocytes. These findings demonstrate that morphine has the potential to alter the glomerular filtration barrier by compromising the integrity of podocytes. Public Library of Science 2013-03-29 /pmc/articles/PMC3612045/ /pubmed/23555556 http://dx.doi.org/10.1371/journal.pone.0055748 Text en © 2013 Lan et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lan, Xiqian
Rai, Partab
Chandel, Nirupama
Cheng, Kang
Lederman, Rivka
Saleem, Moin A.
Mathieson, Peter W.
Husain, Mohammad
Crosson, John T.
Gupta, Kalpna
Malhotra, Ashwani
Singhal, Pravin C.
Morphine Induces Albuminuria by Compromising Podocyte Integrity
title Morphine Induces Albuminuria by Compromising Podocyte Integrity
title_full Morphine Induces Albuminuria by Compromising Podocyte Integrity
title_fullStr Morphine Induces Albuminuria by Compromising Podocyte Integrity
title_full_unstemmed Morphine Induces Albuminuria by Compromising Podocyte Integrity
title_short Morphine Induces Albuminuria by Compromising Podocyte Integrity
title_sort morphine induces albuminuria by compromising podocyte integrity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612045/
https://www.ncbi.nlm.nih.gov/pubmed/23555556
http://dx.doi.org/10.1371/journal.pone.0055748
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