Evidence map›Paper›PMID 41532698›Full record

ArticleClinical and translational medicine2026

Targeting the lactylation of ENO1 alleviates endothelial dysfunction in sepsis.

Xueru Xie, Tingyan Liu, Caiyan Zhang, Ye Cheng, Yajing Gao, Wenfeng Xiao, Haiyan Guo, Yutong Zhou, Yawei Yu, Kexin Wang and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical and translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
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

17 authors.

Xueru XieNHC Key Laboratory of Neonatal Diseases, Children's Hospital of Fudan University and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Tingyan LiuDepartment of Critical Care Medicine and Department of Emergency, Children's Hospital of Fudan University, National Children's Medical Center, Fudan University, Shanghai, China.
Caiyan ZhangDepartment of Critical Care Medicine and Department of Emergency, Children's Hospital of Fudan University, National Children's Medical Center, Fudan University, Shanghai, China.
Ye ChengDepartment of Critical Care Medicine and Department of Emergency, Children's Hospital of Fudan University, National Children's Medical Center, Fudan University, Shanghai, China.
Yajing GaoNHC Key Laboratory of Neonatal Diseases, Children's Hospital of Fudan University and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Wenfeng XiaoNHC Key Laboratory of Neonatal Diseases, Children's Hospital of Fudan University and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Haiyan GuoNHC Key Laboratory of Neonatal Diseases, Children's Hospital of Fudan University and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Yutong ZhouNHC Key Laboratory of Neonatal Diseases, Children's Hospital of Fudan University and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Yawei YuNHC Key Laboratory of Neonatal Diseases, Children's Hospital of Fudan University and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Kexin WangNHC Key Laboratory of Neonatal Diseases, Children's Hospital of Fudan University and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Yinghong LinNHC Key Laboratory of Neonatal Diseases, Children's Hospital of Fudan University and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Lisheng XiaoFujian Key Laboratory of Neonatal Diseases, Xiamen Key Laboratory of Neonatal Diseases, Xiamen Children`s Hospital (Children's Hospital of Fudan University at Xiamen), Xiamen, China.
Yingying ZhangDepartment of Critical Care Medicine and Department of Emergency, Children's Hospital of Fudan University, National Children's Medical Center, Fudan University, Shanghai, China.
Weiguo YangPediatric Intensive Care Unit, Shenzhen Children's Hospital, Shenzhen, China.
Gangfeng YanDepartment of Critical Care Medicine and Department of Emergency, Children's Hospital of Fudan University, National Children's Medical Center, Fudan University, Shanghai, China.
Guoping LuDepartment of Critical Care Medicine and Department of Emergency, Children's Hospital of Fudan University, National Children's Medical Center, Fudan University, Shanghai, China.
Yufeng ZhouNHC Key Laboratory of Neonatal Diseases, Children's Hospital of Fudan University and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

Funding

National Key R&D Program of ChinaNational Natural Science Foundation of ChinaShanghai Committee of Science and TechnologyShanghai Municipal Science and Technology Major ProjectXiamen Key Healthcare Projects
6 · The paper itself

Abstract

backgroundElevated lactate is associated with vascular endothelial dysfunction, a factor that can contribute to organ failure in sepsis. However, the specific mechanisms involved have yet to be fully elucidated. Here, we investigated the role of enolase 1 (ENO1) lactylation in modulating the functions of endothelial cells (ECs) in sepsis pathogenesis.

methodsThe septic mouse model was established using two methods: cecal ligation and puncture (CLP) and intraperitoneal injection of LPS. AAV-ENO1 shRNA was administered to ablate ENO1 in vascular endothelial cells of mice. Tail vein injection of .5% Evans Blue Dye (EBD) was utilised to assess microvascular permeability in septic mice. Post-translational modification (PTM) mass spectrometry was employed to detect key proteins undergoing lactylation in endothelial cells. Additionally, CCK-8 assay, Transwell assay, and scratch wound healing assay were performed to evaluate the fundamental functions of ECs. Further investigations were conducted through Western blotting, Co-immunoprecipitation (CO-IP), RT-qPCR, RNA immunoprecipitation (RIP) and RNA sequencing to examine genes/proteins involved in vascular endothelial injury and their interactions.

resultsWe found that elevated lactate in sepsis promoted the lactylation of ENO1 at the K71 residue, facilitated by the increased activity of the lactyltransferase P300. This modification reduced the binding of TRIM21 mRNA to ENO1, thereby preventing its degradation by limiting the recruitment of CNOT6. Consequently, the stability and expression of TRIM21 mRNA were enhanced. Elevated TRIM21 subsequently binds to vascular endothelial-cadherin (VE-Cadherin), promoting its ubiquitination and degradation, disrupting endothelial adherens junctions (AJs) and increasing endothelial permeability. Targeting the lactylation of ENO1 at K71 with a specific inhibitory peptide alleviated endothelial injury and improved survival rates in septic mice.

conclusionsThese findings suggest that ENO1 lactylation plays a pivotal role in vascular endothelial dysfunction during sepsis. Inhibiting lactylation may offer a therapeutic strategy for sepsis treatment.

Indexed as

DNA-Binding ProteinsEndothelial CellsEndothelium, VascularPhosphopyruvate HydrataseSepsisTumor Suppressor ProteinsAnimalsDisease Models, AnimalHumansMaleMiceMice, Inbred C57BLDNA-Binding ProteinsEno1 protein, mousePhosphopyruvate HydrataseTumor Suppressor Proteinsendothelial dysfunctionENO1lactylationsepsis

Identifiers

PMID41532698
PMCPMC12801394

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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.