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Diacylglycerol kinase epsilon protects against renal ischemia/reperfusion injury in mice through Krüppel-like factor 15/klotho pathway
Although recent studies have indicated that mutations in the gene encoding diacylglycerol kinase epsilon (DGKE) result in some proteinuria related hereditary kidney diseases, the DGKE expression pattern in the kidney and its contribution to acute kidney injury (AKI) remain unknown. Therefore, the pr...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154760/ https://www.ncbi.nlm.nih.gov/pubmed/35616094 http://dx.doi.org/10.1080/0886022X.2022.2079524 |
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author | Wang, Ziying Zhou, Zhuanli Zhang, Yanan Zuo, Fuwen Du, Junyao Wang, Mingwei Hu, Muchen Sun, Yu Wang, Xiaojie Liu, Min Zhang, Yan Tang, Wei Yi, Fan |
author_facet | Wang, Ziying Zhou, Zhuanli Zhang, Yanan Zuo, Fuwen Du, Junyao Wang, Mingwei Hu, Muchen Sun, Yu Wang, Xiaojie Liu, Min Zhang, Yan Tang, Wei Yi, Fan |
author_sort | Wang, Ziying |
collection | PubMed |
description | Although recent studies have indicated that mutations in the gene encoding diacylglycerol kinase epsilon (DGKE) result in some proteinuria related hereditary kidney diseases, the DGKE expression pattern in the kidney and its contribution to acute kidney injury (AKI) remain unknown. Therefore, the present study was designed to detect the role of DGKE in mice with AKI. DGKE expression was time-dependently altered in the kidneys of mice with renal ischemia/reperfusion injury (IRI). Compared with wild-type (WT) mice, DGKE- overexpressing mice (Rosa26-Dgke(+/+)) exhibited protective effects against renal IRI, including reduced serum creatinine, blood urea concentration, tubular cell death and inflammatory responses as well as improved morphological injuries. Consistently, in vitro, DGKE overexpression in human renal proximal tubule (HK-2) cells also protected against oxygen-glucose deprivation (OGD)/reoxygenation-induced cell death. Mechanistically, DGKE regulated Klotho expression, at least partly via the transcription factor Krüppel-like factor (KLF) 15. Moreover, a significant reduction in DGKE was also found in kidneys from patients with ischemia-associated acute tubular necrosis (ATN). Collectively, our studies demonstrate that DGKE protects against AKI in mice at least partly through KLF15/Klotho signaling pathway, indicating that DGKE may present an innovative therapeutic strategy for treating patients with AKI. |
format | Online Article Text |
id | pubmed-9154760 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-91547602022-06-01 Diacylglycerol kinase epsilon protects against renal ischemia/reperfusion injury in mice through Krüppel-like factor 15/klotho pathway Wang, Ziying Zhou, Zhuanli Zhang, Yanan Zuo, Fuwen Du, Junyao Wang, Mingwei Hu, Muchen Sun, Yu Wang, Xiaojie Liu, Min Zhang, Yan Tang, Wei Yi, Fan Ren Fail Laboratory Study Although recent studies have indicated that mutations in the gene encoding diacylglycerol kinase epsilon (DGKE) result in some proteinuria related hereditary kidney diseases, the DGKE expression pattern in the kidney and its contribution to acute kidney injury (AKI) remain unknown. Therefore, the present study was designed to detect the role of DGKE in mice with AKI. DGKE expression was time-dependently altered in the kidneys of mice with renal ischemia/reperfusion injury (IRI). Compared with wild-type (WT) mice, DGKE- overexpressing mice (Rosa26-Dgke(+/+)) exhibited protective effects against renal IRI, including reduced serum creatinine, blood urea concentration, tubular cell death and inflammatory responses as well as improved morphological injuries. Consistently, in vitro, DGKE overexpression in human renal proximal tubule (HK-2) cells also protected against oxygen-glucose deprivation (OGD)/reoxygenation-induced cell death. Mechanistically, DGKE regulated Klotho expression, at least partly via the transcription factor Krüppel-like factor (KLF) 15. Moreover, a significant reduction in DGKE was also found in kidneys from patients with ischemia-associated acute tubular necrosis (ATN). Collectively, our studies demonstrate that DGKE protects against AKI in mice at least partly through KLF15/Klotho signaling pathway, indicating that DGKE may present an innovative therapeutic strategy for treating patients with AKI. Taylor & Francis 2022-05-26 /pmc/articles/PMC9154760/ /pubmed/35616094 http://dx.doi.org/10.1080/0886022X.2022.2079524 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Laboratory Study Wang, Ziying Zhou, Zhuanli Zhang, Yanan Zuo, Fuwen Du, Junyao Wang, Mingwei Hu, Muchen Sun, Yu Wang, Xiaojie Liu, Min Zhang, Yan Tang, Wei Yi, Fan Diacylglycerol kinase epsilon protects against renal ischemia/reperfusion injury in mice through Krüppel-like factor 15/klotho pathway |
title | Diacylglycerol kinase epsilon protects against renal ischemia/reperfusion injury in mice through Krüppel-like factor 15/klotho pathway |
title_full | Diacylglycerol kinase epsilon protects against renal ischemia/reperfusion injury in mice through Krüppel-like factor 15/klotho pathway |
title_fullStr | Diacylglycerol kinase epsilon protects against renal ischemia/reperfusion injury in mice through Krüppel-like factor 15/klotho pathway |
title_full_unstemmed | Diacylglycerol kinase epsilon protects against renal ischemia/reperfusion injury in mice through Krüppel-like factor 15/klotho pathway |
title_short | Diacylglycerol kinase epsilon protects against renal ischemia/reperfusion injury in mice through Krüppel-like factor 15/klotho pathway |
title_sort | diacylglycerol kinase epsilon protects against renal ischemia/reperfusion injury in mice through krüppel-like factor 15/klotho pathway |
topic | Laboratory Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154760/ https://www.ncbi.nlm.nih.gov/pubmed/35616094 http://dx.doi.org/10.1080/0886022X.2022.2079524 |
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