Evidence mapPaperPMID 40347321Full record

ArticleApoptosis : an international journal on programmed cell death2025

Inhibition of SIRT1/HSF1 pathway contributes to doxorubicin-induced nephrotoxicity in ovarian tumor-bearing mice.

Mo Chen, Ying Zhao, Song Hu, Jun-Bo Yuan, Kang-Jie Xie, Shu-Nv Cai, Xiao-Yan Zhu, Jian-Kui Du, Ping-Bo Xu

Abstract read
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In one paragraph

Article in Apoptosis : an international journal on programmed cell death, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Mo Chen *Department of Anesthesiology, Zhejiang Cancer Hospital, Laboratory of Anesthesia and Perioperative Medicine, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China.
Ying Zhao *Department of Anesthesiology, Zhejiang Cancer Hospital, Laboratory of Anesthesia and Perioperative Medicine, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China.
Song Hu *Department of Anesthesiology, Zhejiang Cancer Hospital, Laboratory of Anesthesia and Perioperative Medicine, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China.
Jun-Bo YuanDepartment of Anesthesiology, Zhejiang Cancer Hospital, Laboratory of Anesthesia and Perioperative Medicine, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China.
Kang-Jie XieDepartment of Anesthesiology, Zhejiang Cancer Hospital, Laboratory of Anesthesia and Perioperative Medicine, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China.
Shu-Nv CaiDepartment of Anesthesiology, Zhejiang Cancer Hospital, Laboratory of Anesthesia and Perioperative Medicine, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China.
Xiao-Yan ZhuDepartment of Physiology, Navy Medical University, 800 Xiangyin Road, Shanghai, 200433, China.
Jian-Kui DuDepartment of Physiology, Navy Medical University, 800 Xiangyin Road, Shanghai, 200433, China. dujiankuismmu@126.com.
Ping-Bo XuDepartment of Anesthesiology, Zhejiang Cancer Hospital, Laboratory of Anesthesia and Perioperative Medicine, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China. zzmzkxpb@163.com.

Funding

Hangzhou Institute of Medicine Chinese Academy of Sciences 2024ZZBS13National Natural Science Foundation of China 82000797Zhejiang medical and health science and technology project 2021ky103Zhejiang Traditional Chinese Medicine Science and Technology Plan 2023ZL302 to KJX
6 · The paper itself

Abstract

Doxorubicin (DOX) is a common drug used in chemotherapy to treat for advanced ovarian cancer, but it can cause organ damage, particularly to the kidneys. This study aimed to investigate whether the SIRT1/HSF1 pathway is associated with DOX-induced nephrotoxicity. Bioinformatics analysis was performed using single-cell RNA sequencing (scRNA-seq) data from DOX-treated kidneys to investigate the potential mechanism of DOX-induced renal damage. To explore the role of HSF1 in DOX-induced nephrotoxicity, the lentivirus HSF1 (Lv-HSF1) was injected after tumor implantation, followed by DOX administration. DOX prevented ovarian tumor growth but caused renal injury in mice, as evidenced by elevated UACR, increased blood BUN levels, and abnormalities in kidney structure and fibrosis. Bioinformatic analysis revealed fewer podocytes in the kidneys of DOX-exposed mice than in those of control mice, which was further confirmed by examining renal tissue and murine podocyte cells. Gene set enrichment analysis revealed significant enrichment of HSF1-dependent transactivation and HSF1 activation pathways specifically within podocytes obtained from DOX-treated mice, which was also validated in renal tissue samples. Furthermore, HSF1A attenuated DOX-induced podocyte injury in vitro. Lv-HSF1-targeted podocytes mitigate DOX-induced podocyte injury in vivo. Notably, SIRT1 expression was significantly downregulated in both kidney tissues and podocytes subjected to DOX treatment. The observed damage to podocytes induced by DOX may be attributed to an increase in HSF1 acetylation facilitated through the downregulation of SIRT1, a process that can be counteracted by the administration of the SIRT1 agonist RSV. Collectively, these findings demonstrated that suppression of the SIRT1/HSF1 signaling pathway contributes to DOX-mediated nephrotoxicity in mice bearing ovarian tumors.

Indexed as

DoxorubicinHeat Shock Transcription FactorsOvarian NeoplasmsSirtuin 1AnimalsCell Line, TumorFemaleHumansKidneyMicePodocytesSignal TransductionDoxorubicinHeat Shock Transcription FactorsHsf1 protein, mouseSirt1 protein, mouseSirtuin 1DoxorubicinHSF1NephrotoxicityRSVSIRT1

Identifiers

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.