Evidence map›Paper›PMID 24507193›Full record

ArticleNeuron2014

Astrocyte-derived endothelin-1 inhibits remyelination through notch activation.

Timothy R Hammond, Ana Gadea, Jeff Dupree, Christophe Kerninon, Brahim Nait-Oumesmar, Adan Aguirre, Vittorio Gallo

Erratum issuedAbstract read
In one paragraph

Article in Neuron, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 117 papers.

0numbers the graph read from it
0cells of the map it votes in
117citing 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

117 citing papers in PubMed.

  1. Article
  2. Rethinking MS Therapeutics: From Disease Pathogenesis Mechanisms to AI-Driven Drug Discovery.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026
    Review
  3. In vivo mapping of cortical amyloid beta-myelin coupling in preclinical Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Astrocytic ET-1 System Determines Microglia Phenotype Following Spinal Cord Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  14. Spinal Cord Injury Remyelination: Pathways to Therapies.International journal of molecular sciences · 2025
    Review
  15. EDNRB2 regulates fate, migration, and maturation of hair cell precursors in regenerating avian auditory epithelium explants.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  16. Review
  17. Article
  18. Review
  19. Review
  20. Review

57 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

7 authors.

Timothy R HammondCenter for Neuroscience Research, Children's National Medical Center, Washington, DC 20010, USA; Institute for Biomedical Sciences, The George Washington University, Washington, DC 20052, USA.
Ana GadeaCenter for Neuroscience Research, Children's National Medical Center, Washington, DC 20010, USA.
Jeff DupreeDepartment of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA 23284, USA.
Christophe KerninonCentre de Recherche de l'Institut du Cerveauet de la Moelle Epinière, Inserm U.975; Université Pierre et Marie Curie-Paris 6 UMR-S975; CNRS UMR 7225; and AP-HP Groupe Hospitalier Pitié-Salpêtrière, Fédération de Neurologie, Cedex 13, Paris, France.
Brahim Nait-OumesmarCentre de Recherche de l'Institut du Cerveauet de la Moelle Epinière, Inserm U.975; Université Pierre et Marie Curie-Paris 6 UMR-S975; CNRS UMR 7225; and AP-HP Groupe Hospitalier Pitié-Salpêtrière, Fédération de Neurologie, Cedex 13, Paris, France.
Adan AguirrePharmacological Sciences Department, SUNY at Stony Brook University, Stony Brook, NY 11794, USA.
Vittorio GalloCenter for Neuroscience Research, Children's National Medical Center, Washington, DC 20010, USA; Institute for Biomedical Sciences, The George Washington University, Washington, DC 20052, USA. Electronic address: vgallo@cnmcresearch.org.

Funding

NEUROIMAGING COREP30HD040677 · NICHD · CHILDREN'S RESEARCH INSTITUTE · PI VITTORIO GALLO, VITTORIO GALLO VITTORIO GALLO · 2001 to 2015
$15.9M
A Common Glial-Neuronal Progenitor in Postnatal BrainR01NS045702 · NINDS · CHILDREN'S RESEARCH INSTITUTE · PI VITTORIO GALLO, VITTORIO GALLO VITTORIO GALLO · 2004 to 2014
$3.7M
Characterization of Sox17 as a Regulator of Oligodendrocyte Cell DifferentiationR01NS056427 · NINDS · CHILDREN'S RESEARCH INSTITUTE · PI VITTORIO GALLO, VITTORIO GALLO VITTORIO GALLO · 2007 to 2011
$1.8M
ROLE OF NG2 CELLS IN THE MAINTENANCE OF THE SUBVENTRICULAR ZONE NICHER00NS057944 · NINDS · STATE UNIVERSITY NEW YORK STONY BROOK · PI AGUIRRE, ADAN A · 2010 to 2012
$707k
NICHD NIH HHS P30 HD040677NICHD NIH HHS P30HD40677NINDS NIH HHS R00 NS057944NINDS NIH HHS R01 NS045702NINDS NIH HHS R01NS045702NINDS NIH HHS R01 NS056427NINDS NIH HHS R01NS056427
6 · The paper itself

Abstract

Oligodendrocyte progenitor cells (OPCs) can repair demyelinated lesions by maturing into myelin-producing oligodendrocytes. However, the OPC potential to differentiate can be prevented by inhibitory signals present in the pathological lesion environment. Identification of these signals is essential to promote OPC differentiation and lesion repair. We identified an endogenous inhibitor of remyelination, Endothelin-1 (ET-1), which is highly expressed in reactive astrocytes of demyelinated lesions. Using both gain- and loss-of-function approaches, we demonstrate that ET-1 drastically reduces the rate of remyelination. We also discovered that ET-1 acts mechanistically by promoting Notch activation in OPCs during remyelination through induction of Jagged1 expression in reactive astrocytes. Pharmacological inhibition of ET signaling prevented Notch activation in demyelinated lesions and accelerated remyelination. These findings reveal that ET-1 is a negative regulator of OPC differentiation and remyelination and is potentially a therapeutic target to promote lesion repair in demyelinated tissue.

Indexed as

AnimalsAstrocytesCalcium-Binding ProteinsCell CountCell DifferentiationDemyelinating DiseasesDisease Models, AnimalDrug Delivery SystemsEndothelin-1Gene Expression RegulationGlial Fibrillary Acidic ProteinGreen Fluorescent ProteinsIntercellular Signaling Peptides and ProteinsJagged-1 ProteinLipopolysaccharidesMembrane ProteinsCalcium-Binding ProteinsEndothelin-1Glial Fibrillary Acidic ProteinGreen Fluorescent ProteinsIntercellular Signaling Peptides and ProteinsJag1 protein, mouseJagged-1 ProteinLipopolysaccharidesMembrane ProteinsOligopeptidesPD 142893Platelet Endothelial Cell Adhesion Molecule-1Receptors, NotchSerrate-Jagged Proteins

Identifiers

PMID24507193
PMCPMC3935216

What OpenQuestion holds

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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 OpenQuestion graph.