Evidence map›Paper›PMID 40546121›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

FOXM1 Protects Against Myocardial Ischemia-Reperfusion Injury in Rodent and Porcine Models by Suppressing MKRN1-Dependent LKB1 Ubiquitination.

Shuai Song, Xiaokai Zhang, Zihang Huang, Zhiqiang Pei, Linqi Zeng, Fengze Cai, Tongyao Wang, Mohan Li, Chenyan Liu, Yining Song and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

18 authors.

Shuai SongDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China.
Xiaokai ZhangDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China.
Zihang HuangDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China.
Zhiqiang PeiDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China.
Linqi ZengDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China.
Fengze CaiDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China.
Tongyao WangDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China.
Mohan LiDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China.
Chenyan LiuDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China.
Yining SongDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China.
Jiahao GuoXinxiang Medical University, Henan, 453003, China.
Hao LuDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China.
Xinyu WengDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China.
Li ShenDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China.
Xiaochun ZhangDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China.
Xingxing CaiDepartment of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China.
Aijun SunDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China.
Junbo GeDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China.ORCID https://orcid.org/0000-0002-9360-7332

Funding

Basic Science Center Project T2288101National Natural Science Foundation of China 82370261Shanghai Clinical Research Center for Interventional Medicine 19MC1910300
6 · The paper itself

Abstract

Mitochondrial dysfunction is related to etiopathogenesis and progression of heart failure (HF). The underlying molecular mechanisms are not fully understood. Transcription factor FOXM1 plays an essential role in cardiovascular development. The present study explores its role in mitochondrial bioenergetics in postmitotic cardiomyocytes (CMs). FOXM1 is significantly upregulated in ischemic heart tissues from humans, mice, and pigs. CM-specific Foxm1-knockout mice exhibit dilated cardiomyopathy features associated with mitochondrial dysfunction. Transcriptomic and proteomic profiling of Foxm1-knockout mice reveal robust, specific downregulation of gene programs important for mitochondrial energetics and homeostasis. Analysis of proteome and ubiquitinome data reveal that FOXM1 deficiency in CMs promotes LKB1 ubiquitination and impairs the AMPK signaling and energy metabolism pathways. Bioinformatics analysis identifies that E3 ligase MKRN1 promotes the K48-linked ubiquitination of LKB1 on Lys146, which in turn, inhibits the AMPK signaling pathway and impairs energy homeostasis in mice with HF. CM-specific Mkrn1 knockout ameliorates cardiac dysfunction by rejuvenating the impaired mitochondrial bioenergetics induced by FOXM1 deficiency. FOXM1 overexpression preserves mitochondrial bioenergetics and protects against myocardial I/R injury in both rodent and porcine models. In conclusion, FOXM1 is actively involved in mitochondrial bioenergetics during HF. FOXM1 may be a potential promising therapeutic target for myocardial I/R injury and HF.

Indexed as

Forkhead Box Protein M1Myocardial Reperfusion InjuryProtein Serine-Threonine KinasesUbiquitin-Protein LigasesAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesAnimalsDisease Models, AnimalEnergy MetabolismHumansMaleMiceMice, Inbred C57BLMice, KnockoutMyocytes, CardiacSignal TransductionAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesForkhead Box Protein M1Foxm1 protein, mouseProtein Serine-Threonine KinasesStk11 protein, mouseUbiquitin-Protein LigasesAMPKcardiomyocytesFOXM1heart failuremitochondria

Identifiers

PMID40546121
PMCPMC12463072

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Registered trials

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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 OpenQuestion graph.