SETDB1 targeting SESN2 regulates mitochondrial damage and oxidative stress in renal ischemia-reperfusion injury.

IF 4.4 1区生物学 Q1 BIOLOGY

BMC Biology Pub Date : 2024-10-23 DOI:10.1186/s12915-024-02048-z

Kang Xia, Yumin Hui, Long Zhang, Qiangmin Qiu, Jiacheng Zhong, Hui Chen, Xiuheng Liu, Lei Wang, Zhiyuan Chen

{"title":"SETDB1 targeting SESN2 regulates mitochondrial damage and oxidative stress in renal ischemia-reperfusion injury.","authors":"Kang Xia, Yumin Hui, Long Zhang, Qiangmin Qiu, Jiacheng Zhong, Hui Chen, Xiuheng Liu, Lei Wang, Zhiyuan Chen","doi":"10.1186/s12915-024-02048-z","DOIUrl":null,"url":null,"abstract":"Background: The role of histone methyltransferase SETDB1 in renal ischemia-reperfusion (I/R) injury has not been explored yet. This study aims to investigate the potential mechanism of SETDB1 in regulating renal I/R injury and its impact on mitochondrial damage and oxidative stress.Methods: The in vivo model of renal I/R in mice and the in vitro model of hypoxia/reoxygenation (H/R) in human renal tubular epithelial cells (HK-2) were constructed to detect the expression of SETDB1. Next, the specific inhibitor (R,R)-59 and knockdown viruses were used to inhibit SETDB1 and verify its effects on mitochondrial damage and oxidative stress. Chromatin immunoprecipitation (ChIP) and coimmunoprecipitation (CoIP) were implemented to explore the in-depth mechanism of SETDB1 regulating renal I/R injury.Results: The study found that SETDB1 had a regulatory role in mitochondrial damage and oxidative stress during renal I/R injury. Notably, SESN2 was identified as a target of SETDB1, and its expression was under the influence of SETDB1. Besides, SESN2 mediated the regulation of SETDB1 on renal I/R injury. Through deeper mechanistic studies, we uncovered that SETDB1 collaborates with heterochromatin HP1β, facilitating the labeling of H3K9me3 on the SESN2 promoter and impeding SESN2 expression.Conclusions: The SETDB1/HP1β-SESN2 axis emerges as a potential therapeutic strategy for mitigating renal I/R injury.","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"22 1","pages":"246"},"PeriodicalIF":4.4000,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515507/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s12915-024-02048-z","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: The role of histone methyltransferase SETDB1 in renal ischemia-reperfusion (I/R) injury has not been explored yet. This study aims to investigate the potential mechanism of SETDB1 in regulating renal I/R injury and its impact on mitochondrial damage and oxidative stress.

Methods: The in vivo model of renal I/R in mice and the in vitro model of hypoxia/reoxygenation (H/R) in human renal tubular epithelial cells (HK-2) were constructed to detect the expression of SETDB1. Next, the specific inhibitor (R,R)-59 and knockdown viruses were used to inhibit SETDB1 and verify its effects on mitochondrial damage and oxidative stress. Chromatin immunoprecipitation (ChIP) and coimmunoprecipitation (CoIP) were implemented to explore the in-depth mechanism of SETDB1 regulating renal I/R injury.

Results: The study found that SETDB1 had a regulatory role in mitochondrial damage and oxidative stress during renal I/R injury. Notably, SESN2 was identified as a target of SETDB1, and its expression was under the influence of SETDB1. Besides, SESN2 mediated the regulation of SETDB1 on renal I/R injury. Through deeper mechanistic studies, we uncovered that SETDB1 collaborates with heterochromatin HP1β, facilitating the labeling of H3K9me3 on the SESN2 promoter and impeding SESN2 expression.

Conclusions: The SETDB1/HP1β-SESN2 axis emerges as a potential therapeutic strategy for mitigating renal I/R injury.

查看原文本刊更多论文

SETDB1靶向SESN2调节肾缺血再灌注损伤中的线粒体损伤和氧化应激。

背景：组蛋白甲基转移酶SETDB1在肾缺血再灌注（I/R）损伤中的作用尚未探明。本研究旨在探讨 SETDB1 调节肾脏 I/R 损伤的潜在机制及其对线粒体损伤和氧化应激的影响：方法：构建小鼠肾脏 I/R 体内模型和人肾小管上皮细胞（HK-2）缺氧/再缺氧（H/R）体外模型，检测 SETDB1 的表达。接着，使用特异性抑制剂（R,R）-59 和基因敲除病毒抑制 SETDB1，并验证其对线粒体损伤和氧化应激的影响。通过染色质免疫沉淀（ChIP）和共免疫沉淀（CoIP），深入探讨了SETDB1调控肾脏I/R损伤的机制：结果：研究发现，SETDB1在肾脏I/R损伤过程中对线粒体损伤和氧化应激具有调控作用。值得注意的是，SESN2 被确定为 SETDB1 的靶标，且其表达受 SETDB1 的影响。此外，SESN2还介导了SETDB1对肾脏I/R损伤的调控。通过更深入的机理研究，我们发现SETDB1与异染色质HP1β合作，促进了SESN2启动子上H3K9me3的标记，阻碍了SESN2的表达：SETDB1/HP1β-SESN2轴是减轻肾脏I/R损伤的潜在治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

BMC Biology 生物-生物学

CiteScore

7.80

自引率

1.90%

发文量

260

审稿时长

3 months

期刊介绍： BMC Biology is a broad scope journal covering all areas of biology. Our content includes research articles, new methods and tools. BMC Biology also publishes reviews, Q&A, and commentaries.