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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...

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Autores principales: Fan, Yu, Yuan, Yangmian, Xiong, Mingrui, Jin, Muchuan, Zhang, Donge, Yang, Dong, Liu, Chengyu, Petersen, Robert B., Huang, Kun, Peng, Anlin, Zheng, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2023
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.
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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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