Evidence mapPaperPMID 33257646Full record

ArticleNature communications2020

BETs inhibition attenuates oxidative stress and preserves muscle integrity in Duchenne muscular dystrophy.

Marco Segatto, Roberta Szokoll, Raffaella Fittipaldi, Cinzia Bottino, Lorenzo Nevi, Kamel Mamchaoui, Panagis Filippakopoulos, Giuseppina Caretti

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

33 citing papers in PubMed, 55 citations in OpenAlex.

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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

8 authors at 4 institutions in 3 countries.

Marco SegattoDepartment of Biosciences, Università degli Studi di Milano, Via Celoria 26, 20133, Milan, Italy.
Roberta SzokollDepartment of Biosciences, Università degli Studi di Milano, Via Celoria 26, 20133, Milan, Italy.
Raffaella FittipaldiDepartment of Biosciences, Università degli Studi di Milano, Via Celoria 26, 20133, Milan, Italy.
Cinzia BottinoDepartment of Biosciences, Università degli Studi di Milano, Via Celoria 26, 20133, Milan, Italy.
Lorenzo NeviDepartment of Biosciences, Università degli Studi di Milano, Via Celoria 26, 20133, Milan, Italy.ORCID 0000-0003-0924-2551
Kamel MamchaouiSorbonne Université, Inserm, Institut de Myologie, U974, Center for Research in Myology, 47 Boulevard de l'hôpital, 75013, Paris, France.
Panagis FilippakopoulosStructural Genomics Consortium, Old Road Campus Research Building, Nuffield Department of Medicine, Oxford, OX3 7DQ, UK.
Giuseppina CarettiDepartment of Biosciences, Università degli Studi di Milano, Via Celoria 26, 20133, Milan, Italy. giuseppina.caretti@unimi.it.ORCID 0000-0002-2322-6008
University of Milan · ITInserm · FROpen Data Institute · GBUniversity of Molise · IT

Funding

Medical Research Council MR/N010051/1
6 · The paper itself

Abstract

Duchenne muscular dystrophy (DMD) affects 1 in 3500 live male births. To date, there is no effective cure for DMD, and the identification of novel molecular targets involved in disease progression is important to design more effective treatments and therapies to alleviate DMD symptoms. Here, we show that protein levels of the Bromodomain and extra-terminal domain (BET) protein BRD4 are significantly increased in the muscle of the mouse model of DMD, the mdx mouse, and that pharmacological inhibition of the BET proteins has a beneficial outcome, tempering oxidative stress and muscle damage. Alterations in reactive oxygen species (ROS) metabolism are an early event in DMD onset and they are tightly linked to inflammation, fibrosis, and necrosis in skeletal muscle. By restoring ROS metabolism, BET inhibition ameliorates these hallmarks of the dystrophic muscle, translating to a beneficial effect on muscle function. BRD4 direct association to chromatin regulatory regions of the NADPH oxidase subunits increases in the mdx muscle and JQ1 administration reduces BRD4 and BRD2 recruitment at these regions. JQ1 treatment reduces NADPH subunit transcript levels in mdx muscles, isolated myofibers and DMD immortalized myoblasts. Our data highlight novel functions of the BET proteins in dystrophic skeletal muscle and suggest that BET inhibitors may ameliorate the pathophysiology of DMD.

Indexed as

AnimalsAzepinesBromodomain Containing ProteinsDisease Models, AnimalInflammationMiceMice, Inbred C57BLMice, Inbred mdxMuscle, SkeletalMuscular Dystrophy, DuchenneNADPNADPH OxidasesNeuromuscular DiseasesNuclear ProteinsOxidative StressReactive Oxygen SpeciesAzepinesBrd4 protein, mouseBromodomain Containing Proteins(+)-JQ1 compoundNADPNADPH OxidasesNuclear ProteinsReactive Oxygen SpeciesTranscription FactorsTriazoles

Identifiers

PMID33257646
PMCPMC7705749
OpenAlexW3107705247

What Socratic holds

Textmetadata
LicenceCC BY
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.