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Tet1 deficiency exacerbates oxidative stress in acute kidney injury by regulating superoxide dismutase
Rationale: Increased methylation of key genes has been observed in kidney diseases, suggesting that the ten-eleven translocation (Tet) methyl-cytosine dioxygenase family as well as 5mC oxidation may play important roles. As a member of the Tet family, the role of Tet1 in acute kidney injury (AKI) re...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614682/ https://www.ncbi.nlm.nih.gov/pubmed/37908721 http://dx.doi.org/10.7150/thno.87416 |
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author | Fan, Yu Yuan, Yangmian Xiong, Mingrui Jin, Muchuan Zhang, Donge Yang, Dong Liu, Chengyu Petersen, Robert B. Huang, Kun Peng, Anlin Zheng, Ling |
author_facet | Fan, Yu Yuan, Yangmian Xiong, Mingrui Jin, Muchuan Zhang, Donge Yang, Dong Liu, Chengyu Petersen, Robert B. Huang, Kun Peng, Anlin Zheng, Ling |
author_sort | Fan, Yu |
collection | PubMed |
description | Rationale: Increased methylation of key genes has been observed in kidney diseases, suggesting that the ten-eleven translocation (Tet) methyl-cytosine dioxygenase family as well as 5mC oxidation may play important roles. As a member of the Tet family, the role of Tet1 in acute kidney injury (AKI) remains unclear. Methods: Tet1 knockout mice, with or without tempol treatment, a scavenger of reactive oxygen species (ROS), were challenged with ischemia and reperfusion (I/R) injury or unilateral ureteral obstruction (UUO) injury. RNA-sequencing, Western blotting, qRT-PCR, bisulfite sequencing, chromatin immunoprecipitation, immunohistochemical staining, and dot blot assays were performed. Results: Tet1 expression was rapidly upregulated following I/R or UUO injury. Moreover, Tet1 knockout mice showed increased renal injury and renal cell death, increased ROS accumulation, G2/M cell cycle arrest, inflammation, and fibrosis. Severe renal damage in injured Tet1 knockout mice was alleviated by tempol treatment. Mechanistically, Tet1 reduced the 5mC levels in an enzymatic activity-dependent manner on the promoters of Sod1 and Sod2 to promote their expression, thus lowering injury-induced excessive ROS and reducing I/R or UUO injury. Conclusions: Tet1 plays an important role in the development of AKI by promoting SOD expression through a DNA demethylase-dependent mechanism. |
format | Online Article Text |
id | pubmed-10614682 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-106146822023-10-31 Tet1 deficiency exacerbates oxidative stress in acute kidney injury by regulating superoxide dismutase Fan, Yu Yuan, Yangmian Xiong, Mingrui Jin, Muchuan Zhang, Donge Yang, Dong Liu, Chengyu Petersen, Robert B. Huang, Kun Peng, Anlin Zheng, Ling Theranostics Research Paper Rationale: Increased methylation of key genes has been observed in kidney diseases, suggesting that the ten-eleven translocation (Tet) methyl-cytosine dioxygenase family as well as 5mC oxidation may play important roles. As a member of the Tet family, the role of Tet1 in acute kidney injury (AKI) remains unclear. Methods: Tet1 knockout mice, with or without tempol treatment, a scavenger of reactive oxygen species (ROS), were challenged with ischemia and reperfusion (I/R) injury or unilateral ureteral obstruction (UUO) injury. RNA-sequencing, Western blotting, qRT-PCR, bisulfite sequencing, chromatin immunoprecipitation, immunohistochemical staining, and dot blot assays were performed. Results: Tet1 expression was rapidly upregulated following I/R or UUO injury. Moreover, Tet1 knockout mice showed increased renal injury and renal cell death, increased ROS accumulation, G2/M cell cycle arrest, inflammation, and fibrosis. Severe renal damage in injured Tet1 knockout mice was alleviated by tempol treatment. Mechanistically, Tet1 reduced the 5mC levels in an enzymatic activity-dependent manner on the promoters of Sod1 and Sod2 to promote their expression, thus lowering injury-induced excessive ROS and reducing I/R or UUO injury. Conclusions: Tet1 plays an important role in the development of AKI by promoting SOD expression through a DNA demethylase-dependent mechanism. Ivyspring International Publisher 2023-09-25 /pmc/articles/PMC10614682/ /pubmed/37908721 http://dx.doi.org/10.7150/thno.87416 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Fan, Yu Yuan, Yangmian Xiong, Mingrui Jin, Muchuan Zhang, Donge Yang, Dong Liu, Chengyu Petersen, Robert B. Huang, Kun Peng, Anlin Zheng, Ling Tet1 deficiency exacerbates oxidative stress in acute kidney injury by regulating superoxide dismutase |
title | Tet1 deficiency exacerbates oxidative stress in acute kidney injury by regulating superoxide dismutase |
title_full | Tet1 deficiency exacerbates oxidative stress in acute kidney injury by regulating superoxide dismutase |
title_fullStr | Tet1 deficiency exacerbates oxidative stress in acute kidney injury by regulating superoxide dismutase |
title_full_unstemmed | Tet1 deficiency exacerbates oxidative stress in acute kidney injury by regulating superoxide dismutase |
title_short | Tet1 deficiency exacerbates oxidative stress in acute kidney injury by regulating superoxide dismutase |
title_sort | tet1 deficiency exacerbates oxidative stress in acute kidney injury by regulating superoxide dismutase |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614682/ https://www.ncbi.nlm.nih.gov/pubmed/37908721 http://dx.doi.org/10.7150/thno.87416 |
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