Evidence map›Paper›PMID 41856077›Full record

ArticleRedox biology2026

Histone H3K9 lactylation activates the TXNIP/NLRP3 pathway to drive macrophage inflammation after spinal cord injury.

Chaoran Shi, Feifei Yuan, Xingyi Chen, Sheng Xu, Yinghe Ding, Haicheng Wen, Chunyue Duan, Tianding Wu, Hongbin Lu, Jianzhong Hu and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Redox biology, 2026. 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. Review
  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

12 authors.

Chaoran ShiDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Central South University, Changsha, Hunan Province, 410008, China.
Feifei YuanDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Central South University, Changsha, Hunan Province, 410008, China.
Xingyi ChenDepartment of Ophthalmology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, China.
Sheng XuDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Central South University, Changsha, Hunan Province, 410008, China.
Yinghe DingDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Central South University, Changsha, Hunan Province, 410008, China.
Haicheng WenDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Central South University, Changsha, Hunan Province, 410008, China.
Chunyue DuanDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Central South University, Changsha, Hunan Province, 410008, China.
Tianding WuDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Central South University, Changsha, Hunan Province, 410008, China.
Hongbin LuKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Central South University, Changsha, Hunan Province, 410008, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China. Electronic address: hongbinlu@csu.edu.cn.
Jianzhong HuDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Central South University, Changsha, Hunan Province, 410008, China. Electronic address: jianzhonghu@csu.edu.cn.
Jiaqi XuNational Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Central South University, Changsha, Hunan Province, 410008, China; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China. Electronic address: xjq1217@csu.edu.cn.
Liyuan JiangDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Central South University, Changsha, Hunan Province, 410008, China. Electronic address: jiangliyuanxy@csu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Spinal cord injury (SCI) induces metabolic and immune disruptions that impede tissue repair. However, the underlying mechanisms are poorly understood. In this study, we identified lactate accumulation as a critical driver of macrophage-mediated inflammation through histone H3K9 lactylation (H3K9la). Targeted metabolomics revealed elevated serum lactate levels in SCI patients, which were linked to increased glycolysis and lactate dehydrogenase activity. In mice, lactate accumulation after SCI was found to drive histone H3K9la in lesion-infiltrating macrophages and circulating monocytes. Integrated CUT&Tag and RNA-seq analysis revealed that thioredoxin-interacting protein (TXNIP) is a direct H3K9la target that activates the TXNIP-NLRP3 pathway, exacerbating inflammation and impairing mitochondrial function. In vitro, glycolytic inhibition reversed lactate-induced inflammation and mitochondrial dysfunction. In vivo, a hypoxia-responsive peptide inhibitor (H3K9la-pe) selectively reduced macrophage lactylation and inflammation, restored mitochondrial integrity, promoted axon regeneration, and significantly improved functional recovery in SCI mouse model. These findings elucidate a subacute metabolic-epigenetic-inflammatory axis in SCI and highlight that blocking macrophage H3K9la is a promising therapeutic strategy.

Indexed as

Carrier ProteinsHistonesInflammationMacrophagesNLR Family, Pyrin Domain-Containing 3 ProteinSpinal Cord InjuriesThioredoxinsAnimalsDisease Models, AnimalFemaleHumansMaleMiceMitochondriaSignal TransductionCarrier ProteinsHistonesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseThioredoxinsTXNIP protein, humanTxnip protein, mouseH3K9laLactylationMacrophageNeuroinflammationSpinal cord injuryTXNIP

Identifiers

PMID41856077
PMCPMC13010529

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.