Evidence map›Paper›PMID 41028978›Full record

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

Metabolic Interplay in Acute Lung Injury: PARK7 Integrates FADS1/2-Dependent PUFA Metabolism and H3K14 Lactylation to Attenuate Endothelial Ferroptosis and Dysfunction.

Jian Xu, Yuhan Wang, Weiqi Mao, Tianchang Wei, Yufan Li, Juan Song, Cuiping Zhang, Xiaoyan Chen, Cuicui Chen, Qingyuan Xu and 2 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 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

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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

12 authors.

Jian XuShanghai Key Laboratory of Lung Inflammation and Injury, Shanghai Respiratory Research Institute, Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Yuhan WangShanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai Key Laboratory of Lung Inflammation and Injury, Shanghai Respiratory Research Institute, Department of Pulmonary Medicine, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, 200032, China.
Weiqi MaoShanghai Key Laboratory of Lung Inflammation and Injury, Shanghai Respiratory Research Institute, Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Tianchang WeiShanghai Key Laboratory of Lung Inflammation and Injury, Shanghai Respiratory Research Institute, Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Yufan LiShanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai Key Laboratory of Lung Inflammation and Injury, Shanghai Respiratory Research Institute, Department of Pulmonary Medicine, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, 200032, China.
Juan SongShanghai Key Laboratory of Lung Inflammation and Injury, Shanghai Respiratory Research Institute, Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Cuiping ZhangShanghai Key Laboratory of Lung Inflammation and Injury, Shanghai Respiratory Research Institute, Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Xiaoyan ChenShanghai Key Laboratory of Lung Inflammation and Injury, Shanghai Respiratory Research Institute, Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Cuicui ChenShanghai Key Laboratory of Lung Inflammation and Injury, Shanghai Respiratory Research Institute, Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Qingyuan XuShanghai Key Laboratory of Lung Inflammation and Injury, Shanghai Respiratory Research Institute, Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Xu WuShanghai Key Laboratory of Lung Inflammation and Injury, Shanghai Respiratory Research Institute, Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Yuanlin SongShanghai Key Laboratory of Lung Inflammation and Injury, Shanghai Respiratory Research Institute, Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.ORCID https://orcid.org/0000-0003-3373-6631

Funding

National Key Research and Development Program of China 2024YFC3044400National Natural Science Foundation of China 82130001National Natural Science Foundation of China 82272243R&D Program of Guangzhou National Laboratory GZNL2024A02003Science and Technology Commission of Shanghai Municipality 20Z11901000Science and Technology Commission of Shanghai Municipality 22Y11900800Shanghai Municipal Key Clinical Specialty shslczdzk02201Shanghai Municipal Science and Technology Major Project ZD2021CY001Shanghai Three-year Action Plan to Strengthen the Construction of Public Health System GWVI-11.1-18The Construction of Multi-Disciplinary Treatment System for Severe Pneumonia W2020-013
6 · The paper itself

Abstract

Acute respiratory distress syndrome (ARDS) is a severe clinical condition characterized by widespread inflammation and fluid accumulation in the lungs. Endothelial cell (EC) metabolic changes in acute lung injury (ALI) and their relationship to injury remain unclear. Transcriptomic and lipidomic analyses revealed downregulation of PUFA synthesis pathways, particularly omega-3 PUFAs, in pulmonary ECs during LPS-induced ALI. Activation of the PUFA metabolic pathway, through FADS1/2 overexpression or omega-3 fatty acid supplementation, protected ECs from ferroptosis and restored barrier function. In vivo, pulmonary EC-specific overexpression of FADS1/2 contributed to the alleviation of ALI. Overexpression of whole lung FADS1/2, combined with alpha-linolenic acid (ALA) supplementation, also significantly mitigated ALI. PARK7 is identified as an endogenous regulator of FADS1/2, acting through the BMP-BMPR-SMAD1/5/9 signaling. Driven by histone H3K14 lactylation, which is also promoted by the downregulation of FADS1/2, PARK7 upregulation restored FADS1/2 expression and counteracted ferroptosis, thereby forming a protective feedback loop. This study elucidates a novel regulatory axis involving the two major metabolic changes-downregulation of PUFA synthesis and upregulation of histone lactylation-in ALI pathogenesis, which are interconnected through the PARK7-BMP signaling pathway. Targeting this axis offers potential therapeutic strategies for mitigating endothelial dysfunction and ferroptosis in ARDS/ALI.

Indexed as

Acute Lung InjuryCoenzyme A LigasesEndothelial CellsFatty Acid DesaturasesFatty Acids, UnsaturatedFerroptosisHistonesAnimalsDelta-5 Fatty Acid DesaturaseFatty Acids, Omega-3HumansMaleMiceMice, Inbred C57BLSignal TransductionCoenzyme A LigasesDelta-5 Fatty Acid DesaturaseFADS1 protein, humanFADS2 protein, humanFatty Acid DesaturasesFatty Acids, Omega-3Fatty Acids, UnsaturatedHistonesacute lung injury (ALI)endothelial cellferroptosishistone lactylationPARK7polyunsaturated fatty acid (PUFA)

Identifiers

PMID41028978
PMCPMC12697827

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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.