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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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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. |
format | Online Article Text |
id | pubmed-7348052 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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