Evidence map›Paper›PMID 41888366›Full record

ArticleInflammation2026

HIF-1 A-Mediated Lactate Metabolism Confers Ferroptosis Resistance in M1 Macrophages Through Histone Lactylation During Acute Lung Injury.

Juan Xie, Runwei Ma, Cheng Guo, Yang Li, Xinyuan Liu, Xiaoli Yu, Qingming Yang, Kai Liu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Inflammation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

8 authors.

Juan XieYunnan Institute of Pediatrics；Yunnan Key Laboratory of Children's Major Disease Research； Yunnan Province Clinical Research Center for Children's Health and Disease, Kunming Children's Hospital & Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650228, China.
Runwei MaDepartment of Cardiac Surgery, Fuwai Yunnan Hospital, Chinese Academy of Medical Sciences, Affiliated Cardiovascular Hospital of Kunming Medical University, Kunming, Yunnan, 650102, China.
Cheng GuoComprehensive Pediatrics, Kunming Children's Hospital & Affiliated Hospital of Kunming Medical University, No. 28, Shulin Street, Xishan District, Kunming, Yunnan Province, 650032, China.
Yang LiComprehensive Pediatrics, Kunming Children's Hospital & Affiliated Hospital of Kunming Medical University, No. 28, Shulin Street, Xishan District, Kunming, Yunnan Province, 650032, China.
Xinyuan LiuComprehensive Pediatrics, Kunming Children's Hospital & Affiliated Hospital of Kunming Medical University, No. 28, Shulin Street, Xishan District, Kunming, Yunnan Province, 650032, China.
Xiaoli YuComprehensive Pediatrics, Kunming Children's Hospital & Affiliated Hospital of Kunming Medical University, No. 28, Shulin Street, Xishan District, Kunming, Yunnan Province, 650032, China.
Qingming YangComprehensive Pediatrics, Kunming Children's Hospital & Affiliated Hospital of Kunming Medical University, No. 28, Shulin Street, Xishan District, Kunming, Yunnan Province, 650032, China.
Kai LiuComprehensive Pediatrics, Kunming Children's Hospital & Affiliated Hospital of Kunming Medical University, No. 28, Shulin Street, Xishan District, Kunming, Yunnan Province, 650032, China. liukai@kmmu.edu.cn.

Funding

2025 Yunnan Provincial Clinical Medical Center Research Project 2024YNLCYXZX0435Kunming Health Science and Technology Talent Cultivation Program 2024-SW( Backup)-52
6 · The paper itself

Abstract

Background: Acute lung injury (ALI) is characterized by excessive inflammation and oxidative stress, with macrophages playing pivotal roles in disease progression. The differential survival mechanisms of macrophage subsets during ALI remain poorly understood. Methods: We performed integrated analysis of ALI datasets (GSE11434, GSE237260, GSE264032) and isolated CD14 + macrophages from bronchoalveolar lavage fluid of ALI patients. Murine alveolar macrophages (MH-S) were polarized to M1/M2 phenotypes and subjected to ferroptosis induction. HIF-1 A knockdown and lactate supplementation experiments were performed to investigate metabolic regulation. Myeloid-specific HIF-1 A knockout mice were generated and subjected to LPS-induced ALI. Results: Transcriptomic analysis revealed ferroptosis as a key pathway in ALI, with macrophages showing the highest expression of ferroptosis-related genes. ALI-derived macrophages exhibited enhanced ferroptosis-defense gene expression and elevated lactate production. M1 macrophages demonstrated superior ferroptosis resistance compared to M2 macrophages, associated with higher baseline expression of antioxidant genes and enhanced HIF-1 A signaling. Mechanistically, HIF-1 A in M1 macrophages promoted lactate metabolism, which activated ferroptosis-defense genes through histone lactylation. Myeloid-specific HIF-1 A knockout prevented M1 macrophage survival advantage, reduced inflammatory tissue damage, and alleviated ALI severity. Conclusions: HIF-1 A-mediated lactate metabolism confers ferroptosis resistance in M1 macrophages through epigenetic activation of antioxidant defense genes. This metabolic reprogramming represents a novel therapeutic target for modulating macrophage survival and inflammation in ALI.

Indexed as

Acute Lung InjuryFerroptosisHistonesHypoxia-Inducible Factor 1, alpha SubunitLactic AcidMacrophagesMacrophages, AlveolarAnimalsHumansMiceMice, KnockoutHif1a protein, mouseHistonesHypoxia-Inducible Factor 1, alpha SubunitLactic AcidAcute lung injuryFerroptosisHIF-1AHistone lactylationLactate metabolismMacrophage polarization

Identifiers

PMID41888366
PMCPMC13171684

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.