Evidence map›Paper›PMID 40266881›Full record

ArticleJCI insight2025

METTL14 promotes intimal hyperplasia through m6A-mediated control of vascular smooth muscle dedifferentiation genes.

Grace Chensee, Bob Sl Lee, Immanuel D Green, Jessica Tieng, Renhua Song, Natalia Pinello, Quintin Lee, Majid Mehravar, David A Robinson, Mian Wang and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

14 authors.

Grace ChenseeVascular Epigenetics Laboratory, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia.
Bob Sl LeeVascular Epigenetics Laboratory, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia.
Immanuel D GreenEpigenetics and RNA Biology Laboratory, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.
Jessica TiengEpigenetics and RNA Biology Laboratory, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.
Renhua SongEpigenetics and RNA Biology Laboratory, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.
Natalia PinelloEpigenetics and RNA Biology Laboratory, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.
Quintin LeeEpigenetics and RNA Biology Laboratory, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.
Majid MehravarEpigenetics and RNA Biology Laboratory, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.
David A RobinsonRoyal Prince Alfred Hospital, Sydney, New South Wales, Australia.
Mian WangDepartment of Vascular Surgery, National Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, the First Affiliated Hospital for Sun Yat-Sen University, Guangzhou, China.
Mary M KavurmaCentre for Peripheral Artery Disease, Heart Research Institute, Newtown, New South Wales, Australia.
Jun YuCenter for Metabolic Disease Research and Department of Cardiovascular Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, USA.
Justin Jl WongEpigenetics and RNA Biology Laboratory, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.
Renjing LiuVascular Epigenetics Laboratory, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Vascular smooth muscle cells (VSMCs) possess significant phenotypic plasticity, shifting between a contractile phenotype and a synthetic state for vascular repair/remodeling. Dysregulated VSMC transformation, marked by excessive proliferation and migration, primarily drives intimal hyperplasia. N6-methyladenosine (m6A), the most prevalent RNA modification in eukaryotes, plays a critical role in gene expression regulation; however, its impact on VSMC plasticity is not fully understood. We investigated the changes in m6A modification and its regulatory factors during VSMC phenotypic shifts and their influence on intimal hyperplasia. We demonstrate that METTL14, crucial for m6A deposition, significantly promoted VSMC dedifferentiation. METTL14 expression, initially negligible, was elevated in synthetic VSMC cultures, postinjury neointimal VSMCs, and human restenotic arteries. Reducing Mettl14 levels in mouse primary VSMCs decreased prosynthetic genes, suppressing their proliferation and migration. m6A-RIP-seq profiling showed key VSMC gene networks undergo altered m6A regulation in Mettl14-deficient cells. Mettl14 enhanced Klf4 and Serpine1 expression through increased m6A deposition. Local Mettl14 knockdown significantly curbed neointimal formation after arterial injury, and reducing Mettl14 in hyperplastic arteries halted further neointimal development. We show that Mettl14 is a pivotal regulator of VSMC dedifferentiation, influencing Klf4- and Serpine1-mediated phenotypic conversion. Inhibiting METTL14 is a viable strategy for preventing restenosis and halting restenotic occlusions.

Indexed as

Cell DedifferentiationMethyltransferasesMuscle, Smooth, VascularTunica IntimaAdenosineAnimalsCells, CulturedDisease Models, AnimalFemaleFemoral ArteryGene Expression RegulationGraft Occlusion, VascularHumansHyperplasiaKruppel-Like Factor 4MaleAdenosineKruppel-Like Factor 4MethyltransferasesMETTL14 protein, humanMettl14 protein, mouseN-methyladenosinePlasminogen Activator Inhibitor 1Cardiovascular diseaseEpigeneticsGene therapyTherapeuticsVascular biology

Identifiers

PMID40266881
PMCPMC12128973

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.