Evidence map›Paper›PMID 34102854›Full record

ArticleStroke2021

FTO (Fat-Mass and Obesity-Associated Protein) Participates in Hemorrhage-Induced Thalamic Pain by Stabilizing Toll-Like Receptor 4 Expression in Thalamic Neurons.

Ganglan Fu, Shibin Du, Tianfeng Huang, Minghui Cao, Xiaozhou Feng, Shaogen Wu, Sfian Albik, Alex Bekker, Yuan-Xiang Tao

Open access · bronzeAbstract read
In one paragraph

Article in Stroke, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.1field-weighted citation impact, top 12% of its field
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

25 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
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  7. Lysophosphatidic acid receptor 5 in insular cortex as a potential analgesic target in neuropathic pain.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Article
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  14. The mCardiovascular diagnosis and therapy · 2024
    Article
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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

9 authors at 1 institution in 2 countries.

Ganglan Fu *Department of Anesthesiology (G.F., S.D., T.H., M.C., X.F., S.W., S.A., A.B., Y.X.T.), New Jersey Medical School, Rutgers, The State University of New Jersey, Newark.
Shibin Du *Department of Anesthesiology (G.F., S.D., T.H., M.C., X.F., S.W., S.A., A.B., Y.X.T.), New Jersey Medical School, Rutgers, The State University of New Jersey, Newark.
Tianfeng Huang *Department of Anesthesiology (G.F., S.D., T.H., M.C., X.F., S.W., S.A., A.B., Y.X.T.), New Jersey Medical School, Rutgers, The State University of New Jersey, Newark.
Minghui Cao *Department of Anesthesiology (G.F., S.D., T.H., M.C., X.F., S.W., S.A., A.B., Y.X.T.), New Jersey Medical School, Rutgers, The State University of New Jersey, Newark.
Xiaozhou FengDepartment of Anesthesiology (G.F., S.D., T.H., M.C., X.F., S.W., S.A., A.B., Y.X.T.), New Jersey Medical School, Rutgers, The State University of New Jersey, Newark.
Shaogen WuDepartment of Anesthesiology (G.F., S.D., T.H., M.C., X.F., S.W., S.A., A.B., Y.X.T.), New Jersey Medical School, Rutgers, The State University of New Jersey, Newark.
Sfian AlbikDepartment of Anesthesiology (G.F., S.D., T.H., M.C., X.F., S.W., S.A., A.B., Y.X.T.), New Jersey Medical School, Rutgers, The State University of New Jersey, Newark.
Alex BekkerDepartment of Anesthesiology (G.F., S.D., T.H., M.C., X.F., S.W., S.A., A.B., Y.X.T.), New Jersey Medical School, Rutgers, The State University of New Jersey, Newark.
Yuan-Xiang TaoDepartment of Anesthesiology (G.F., S.D., T.H., M.C., X.F., S.W., S.A., A.B., Y.X.T.), New Jersey Medical School, Rutgers, The State University of New Jersey, Newark.
Rutgers, The State University of New Jersey · US

Funding

Discovery and validation of a new long noncoding RNA as a novel target for neuropathic painRF1NS113881 · NINDS · RBHS-NEW JERSEY MEDICAL SCHOOL · PI DAVIDSON, STEVE, TAO, YUAN-XIANG · 2019 to 2019
$3.5M
Role of dorsal root ganglion FTO, a RNA demethylase, in neuropathic painR01NS111553 · NINDS · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI TAO, YUAN-XIANG · 2019 to 2023
$2.5M
Epigenetic regulation of neuropathic pain: Role of DRG histone methyltransferase G9aR01NS094664 · NINDS · RBHS-NEW JERSEY MEDICAL SCHOOL · PI TAO, YUAN-XIANG · 2016 to 2020
$2.0M
NINDS NIH HHS R01 NS094664NINDS NIH HHS R01 NS111553NINDS NIH HHS RF1 NS113881
6 · The paper itself

Abstract

Background and Purpose: Hemorrhage-caused gene changes in the thalamus likely contribute to thalamic pain genesis. RNA N6-methyladenosine modification is an additional layer of gene regulation. Whether FTO (fat-mass and obesity-associated protein), an N6-methyladenosine demethylase, participates in hemorrhage-induced thalamic pain is unknown. Methods: Expression of Fto mRNA and protein was assessed in mouse thalamus after hemorrhage caused by microinjection of Coll IV (type IV collagenase) into unilateral thalamus. Effect of intraperitoneal administration of meclofenamic acid (a FTO inhibitor) or microinjection of adeno-associated virus 5 (AAV5) expressing Cre into the thalamus of Ftofl/fl mice on the Coll IV microinjection–induced TLR4 (Toll-like receptor 4) upregulation and nociceptive hypersensitivity was examined. Effect of thalamic microinjection of AAV5 expressing Fto (AAV5-Fto) on basal thalamic TLR4 expression and nociceptive thresholds was also analyzed. Additionally, level of N6-methyladenosine in Tlr4 mRNA and its binding to FTO or YTHDF2 (YTH N6-methyladenosine RNA binding protein 2) were observed. Results: FTO was detected in neuronal nuclei of thalamus. Level of FTO protein, but not mRNA, was time-dependently increased in the ipsilateral thalamus on days 1 to 14 after Coll IV microinjection. Intraperitoneal injection of meclofenamic acid or adeno-associated virus-5 expressing Cre microinjection into Ftofl/fl mouse thalamus attenuated the Coll IV microinjection–induced TLR4 upregulation and tissue damage in the ipsilateral thalamus and development and maintenance of nociceptive hypersensitivities on the contralateral side. Thalamic microinjection of AAV5-Fto increased TLR4 expression and elicited hypersensitivities to mechanical, heat and cold stimuli. Mechanistically, Coll IV microinjection produced an increase in FTO binding to Tlr4 mRNA, an FTO-dependent loss of N6-methyladenosine sites in Tlr4 mRNA and a reduction in the binding of YTHDF2 to Tlr4 mRNA in the ipsilateral thalamus. Conclusions: Our findings suggest that FTO participates in hemorrhage-induced thalamic pain by stabilizing TLR4 upregulation in thalamic neurons. FTO may be a potential target for the treatment of this disorder.

Indexed as

AdenosineAlpha-Ketoglutarate-Dependent Dioxygenase FTOAnimalsCerebral HemorrhageGene Knockdown TechniquesMaleMiceMice, Inbred C57BLMice, TransgenicMicroinjectionsNeuralgiaNeuronsThalamusToll-Like Receptor 4AdenosineAlpha-Ketoglutarate-Dependent Dioxygenase FTOFTO protein, mouseN-methyladenosineTlr4 protein, mouseToll-Like Receptor 4FTO proteinhemorrhagic strokemeclofenamic acidmicroinjectionsneuronsthalamus

Identifiers

PMID34102854
PMCPMC8423095
OpenAlexW3169315724

What OpenQuestion holds

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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.