Evidence map›Paper›PMID 41106721›Full record

ArticleJournal of advanced research2026

KDM6A/MMP-3 epigenetic axis governs macrophage senescence after spinal cord injury for mediating the regenerative niche to promote neurological repair.

Jinyun Zhao, Xiaolong Sheng, Yinghe Ding, Haicheng Wen, Lifu Zheng, Yi Sun, Rundong He, Chengjun Li, Tian Qin, Tianding Wu and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 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.

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3 · Its place in the literature

Who cites it

3 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

15 authors.

Jinyun ZhaoDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Road 87, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China; Department of Ultrasonography, Xiangya Hospital, Central South University, Changsha 410008, China.
Xiaolong ShengDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Road 87, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China.
Yinghe DingDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Road 87, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China.
Haicheng WenDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Road 87, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China.
Lifu ZhengDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Road 87, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China.
Yi SunDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Road 87, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China.
Rundong HeDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Road 87, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China.
Chengjun LiDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Road 87, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China.
Tian QinDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Road 87, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China.
Tianding WuDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Road 87, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China.
Liyuan JiangDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Road 87, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China.
Hongbin LuKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Road 87, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China.
Yong CaoDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Road 87, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China. Electronic address: xycaoyong@csu.edu.cn.
Jianzhong HuDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Road 87, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China. Electronic address: jianzhonghu@csu.edu.cn.
Chunyue DuanDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Road 87, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, China. Electronic address: docdcy@csu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionSpinal cord injury (SCI) stands as the primary cause of disability, still lacking a clear pathogenesis and effective treatment. The role of macrophages is particularly unclear in SCI, especially regarding cellular senescence. Additionally, the mechanisms driving macrophage senescence after SCI, the release of senescence-associated secretory phenotype (SASP) factors that affect the regenerative niche, and their contributions to SCI progression remain elusive.

objectivesTo investigate the role and underlying mechanism of Ubiquitously transcribed Tetratricopeptide repeat, X chromosome (UTX) in regulating macrophage senescence following SCI.

methodsA contusive SCI model was constructed to explore the presence of senescent macrophages. After screening for UTX by a PCR array, conditioned knockout UTX mice (LysM-Cre; UTX

resultsAn elevated presence of lysine demethylase 6A (KDM6A/UTX), a special epigenetic regulatory modifier, was observed in macrophage senescence after SCI. Conditional deletion of UTX not only prevented macrophage senescence, but also enhanced the formation of a regenerative niche that protected endothelial cells from senescence and improved their proliferation. Mechanistically, UTX epigenetically regulated MMP-3 transcription through demethylating histone H3 lysine di/trimethylation (H3K27me2/3) at its promoter region. This led to senescent macrophages releasing MMP-3, a key SASP factor that disrupts the local microenvironment and impairs spinal cord repair post-injury. Notably, MMP-3 could act as a pro-senescent agent by senescent macrophages to propagate cellular senescence in endothelial cells (ECs), exacerbating cellular senescence in the injured region.

conclusionsOur findings elucidate the KDM6A/MMP-3 epigenetic regulatory axis, which governs macrophage senescence and creates an inhibitory microenvironment for regeneration after SCI. Targeting this pathway promotes angiogenesis and facilitates neural repair, highlighting its potential as a therapeutic target for improving functional recovery after SCI.

Indexed as

Cellular SenescenceEpigenesis, GeneticHistone DemethylasesMacrophagesMatrix Metalloproteinase 3Nerve RegenerationSpinal Cord InjuriesAnimalsDisease Models, AnimalFemaleMiceMice, Inbred C57BLMice, KnockoutHistone DemethylasesMatrix Metalloproteinase 3Mmp3 protein, mouseUtx protein, mouseCellular senescenceEpigenetic regulationSpinal cord injuryUTX

Identifiers

PMID41106721
PMCPMC13316546

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