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Retinoic Acid Alleviates Cisplatin-Induced Acute Kidney Injury Through Activation of Autophagy

Cisplatin-induced acute kidney injury (CIAKI) is a common complication in patients receiving cisplatin-based chemotherapy. But the effective therapies for CIAKI are not available. Retinoic acid (RA), the main derivative of vitamin A, has the potential to reduce inflammation and fibrosis in renal inj...

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Autores principales: Wu, Junxia, Zheng, Canbin, Wan, Xin, Shi, Mingjun, McMillan, Kathryn, Maique, Jenny, Cao, Changchun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348052/
https://www.ncbi.nlm.nih.gov/pubmed/32719599
http://dx.doi.org/10.3389/fphar.2020.00987
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author Wu, Junxia
Zheng, Canbin
Wan, Xin
Shi, Mingjun
McMillan, Kathryn
Maique, Jenny
Cao, Changchun
author_facet Wu, Junxia
Zheng, Canbin
Wan, Xin
Shi, Mingjun
McMillan, Kathryn
Maique, Jenny
Cao, Changchun
author_sort Wu, Junxia
collection PubMed
description Cisplatin-induced acute kidney injury (CIAKI) is a common complication in patients receiving cisplatin-based chemotherapy. But the effective therapies for CIAKI are not available. Retinoic acid (RA), the main derivative of vitamin A, has the potential to reduce inflammation and fibrosis in renal injury. However, the effect and mechanism of RA on CIAKI are still unclear. The aim of this study is to investigate whether RA can alleviate CIAKI through activation of autophagy. In this study, we evaluated the effect of RA, RA’s effect on autophagy and apoptosis after cisplatin-induced injury on renal tubular epithelial cells (RTECs) by LDH assay, immunoblotting and TUNEL staining. Then we established Atg5(flox/flox):Cagg-Cre mice in which Cagg-Cre is tamoxifen inducible, and Atg5 is conditional deleted after tamoxifen injection. The effect of RA and RA’s effect on autophagy on CIAKI model were evaluated by biochemical assessment, hematoxylin and eosin (HE) staining, and immunoblotting in the control and autophagy deficient mice. In vitro, RA protected RTECs against cisplatin-induced injury, activated autophagy, and inhibited cisplatin-induced apoptosis. In vivo, RA attenuated cisplatin-induced tubular damage, shown by improved renal function, decreased renal cast formation, decreased NGAL expression, and activated autophagy in the control mice. Furthermore, the nephrotoxicity of cisplatin was aggravated, and the protective effect of RA was attenuated in autophagy deficient mice, indicating that RA works in an autophagy-dependent manner on CIAKI. RA activates autophagy and alleviates CIAKI in vivo and in vitro.Thus RA may be a renoprotective adjuvant for cisplatin-based chemotherapy.
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spelling pubmed-73480522020-07-26 Retinoic Acid Alleviates Cisplatin-Induced Acute Kidney Injury Through Activation of Autophagy Wu, Junxia Zheng, Canbin Wan, Xin Shi, Mingjun McMillan, Kathryn Maique, Jenny Cao, Changchun Front Pharmacol Pharmacology Cisplatin-induced acute kidney injury (CIAKI) is a common complication in patients receiving cisplatin-based chemotherapy. But the effective therapies for CIAKI are not available. Retinoic acid (RA), the main derivative of vitamin A, has the potential to reduce inflammation and fibrosis in renal injury. However, the effect and mechanism of RA on CIAKI are still unclear. The aim of this study is to investigate whether RA can alleviate CIAKI through activation of autophagy. In this study, we evaluated the effect of RA, RA’s effect on autophagy and apoptosis after cisplatin-induced injury on renal tubular epithelial cells (RTECs) by LDH assay, immunoblotting and TUNEL staining. Then we established Atg5(flox/flox):Cagg-Cre mice in which Cagg-Cre is tamoxifen inducible, and Atg5 is conditional deleted after tamoxifen injection. The effect of RA and RA’s effect on autophagy on CIAKI model were evaluated by biochemical assessment, hematoxylin and eosin (HE) staining, and immunoblotting in the control and autophagy deficient mice. In vitro, RA protected RTECs against cisplatin-induced injury, activated autophagy, and inhibited cisplatin-induced apoptosis. In vivo, RA attenuated cisplatin-induced tubular damage, shown by improved renal function, decreased renal cast formation, decreased NGAL expression, and activated autophagy in the control mice. Furthermore, the nephrotoxicity of cisplatin was aggravated, and the protective effect of RA was attenuated in autophagy deficient mice, indicating that RA works in an autophagy-dependent manner on CIAKI. RA activates autophagy and alleviates CIAKI in vivo and in vitro.Thus RA may be a renoprotective adjuvant for cisplatin-based chemotherapy. Frontiers Media S.A. 2020-07-03 /pmc/articles/PMC7348052/ /pubmed/32719599 http://dx.doi.org/10.3389/fphar.2020.00987 Text en Copyright © 2020 Wu, Zheng, Wan, Shi, McMillan, Maique and Cao http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Wu, Junxia
Zheng, Canbin
Wan, Xin
Shi, Mingjun
McMillan, Kathryn
Maique, Jenny
Cao, Changchun
Retinoic Acid Alleviates Cisplatin-Induced Acute Kidney Injury Through Activation of Autophagy
title Retinoic Acid Alleviates Cisplatin-Induced Acute Kidney Injury Through Activation of Autophagy
title_full Retinoic Acid Alleviates Cisplatin-Induced Acute Kidney Injury Through Activation of Autophagy
title_fullStr Retinoic Acid Alleviates Cisplatin-Induced Acute Kidney Injury Through Activation of Autophagy
title_full_unstemmed Retinoic Acid Alleviates Cisplatin-Induced Acute Kidney Injury Through Activation of Autophagy
title_short Retinoic Acid Alleviates Cisplatin-Induced Acute Kidney Injury Through Activation of Autophagy
title_sort retinoic acid alleviates cisplatin-induced acute kidney injury through activation of autophagy
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348052/
https://www.ncbi.nlm.nih.gov/pubmed/32719599
http://dx.doi.org/10.3389/fphar.2020.00987
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