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

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

  • BMC Biol. 2024 Oct 23;22(1):246. doi: 10.1186/s12915-024-02048-z.
Kang Xia # 1 2 3,  Yumin Hui # 1 3,  Long Zhang # 1 2 3,  Qiangmin Qiu 1 2 3,  Jiacheng Zhong 1 3,  Hui Chen 1 3,  Xiuheng Liu 4 5,  Lei Wang 6 7,  Zhiyuan Chen 8 9
Affiliations

Affiliations

  • 1 Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
  • 2 Department of Organ Transplantation, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
  • 3 Wuhan University Institute of Urological Disease, Wuhan, Hubei, China.
  • 4 Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. drliuxh@hotmail.com.
  • 5 Wuhan University Institute of Urological Disease, Wuhan, Hubei, China. drliuxh@hotmail.com.
  • 6 Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. drwanglei@whu.edu.cn.
  • 7 Wuhan University Institute of Urological Disease, Wuhan, Hubei, China. drwanglei@whu.edu.cn.
  • 8 Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. chenzhiyuan163@163.com.
  • 9 Wuhan University Institute of Urological Disease, Wuhan, Hubei, China. chenzhiyuan163@163.com.
  • # Contributed equally.
PMID: 39443993 DOI: 10.1186/s12915-024-02048-z
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.

Keywords

Mitochondrial damage; Oxidative stress; Renal ischemia–reperfusion injury; SESN2; SETDB1.

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