Evidence map›Paper›PMID 39474980›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024

PKM2-Driven Lactate Overproduction Triggers Endothelial-To-Mesenchymal Transition in Ischemic Flap via Mediating TWIST1 Lactylation.

Yining Xu, Xianhui Ma, Weiyu Ni, Lin Zheng, Zhongnan Lin, Yingying Lai, Ningning Yang, Zhanqiu Dai, Teng Yao, Zeyang Chen and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 1 pooled it
–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

54 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Lactate Signal: Modulator of Cellular Energy Production and Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
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  4. Lactate-Mediated Lysine Lactylation in Renal Fibrosis: Current Progress and Challenges.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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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

15 authors.

Yining XuDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
Xianhui MaDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
Weiyu NiDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Lin ZhengDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
Zhongnan LinDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
Yingying LaiDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
Ningning YangDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
Zhanqiu DaiDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
Teng YaoDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Zeyang ChenDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
Lifeng ShenDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Haitao WangDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Long WangDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
Yizheng WuDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Weiyang GaoDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.ORCID 0000-0002-6987-5206

Funding

China National Postdoctoral Program for Innovative Talents BX20230315Natural Science Foundation of China 81873942Natural Science Foundation of China 82002057Natural Science Foundation of China 82302730Postdoctoral Research Foundation of China 2022M720125
6 · The paper itself

Abstract

The accumulation of lactate is a rising risk factor for patients after flap transplantation. Endothelial-to-mesenchymal transition (EndoMT) plays a critical role in skin fibrosis. Nevertheless, whether lactate overproduction directly contributes to flap necrosis and its mechanism remain unknown. The current study reveals that skin flap mice exhibit enhanced PKM2 and fibrotic response. Endothelial-specific deletion of PKM2 attenuates flap necrosis and ameliorates flap fibrosis in mice. Administration of lactate or overexpressing PKM2 promotes dysfunction of endothelial cells and stimulates mesenchymal-like phenotype following hypoxia. Mechanistically, glycolytic-lactate induces a correlation between Twist1 and p300/CBP, leading to lactylation of Twist1 lysine 150 (K150la). The increase in K150la promotes Twist1 phosphorylation and nuclear translocation and further regulates the transcription of TGFB1, hence inducing fibrosis phenotype. Genetically deletion of endothelial-specific PKM2 in mice diminishes lactate accumulation and Twist1 lactylation, then attenuates EndoMT-associated fibrosis following flap ischemia. The serum lactate levels of flap transplantation patients are elevated and exhibit predictive value for prognosis. This findings suggested a novel role of PKM2-derived lactate in mediating Twist1 lactylation and exacerbates flap fibrosis and ischemia. Inhibition of glycolytic-lactate and Twist1 lactylation reduces flap necrosis and fibrotic response might become a potential therapeutic strategy for flap ischemia.

Indexed as

Nuclear ProteinsThyroid Hormone-Binding ProteinsTwist-Related Protein 1AnimalsCarrier ProteinsDisease Models, AnimalEpithelial-Mesenchymal TransitionFibrosisHumansIschemiaLactic AcidMaleMembrane ProteinsMicePyruvate KinaseSurgical FlapsCarrier ProteinsLactic AcidMembrane ProteinsNuclear ProteinsPkm protein, mousePyruvate KinaseThyroid Hormone-Binding ProteinsThyroid HormonesTwist1 protein, mouseTwist-Related Protein 1endothelial‐to‐mesenchymal transitionlactatelactylationPyruvate kinase M2random‐pattern skin flap

Identifiers

PMID39474980
PMCPMC11653614

What OpenQuestion holds

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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.