Evidence map›Paper›PMID 38310100›Full record

ArticleNature communications2024

The liver and muscle secreted HFE2-protein maintains central nervous system blood vessel integrity.

Xue Fan Wang, Robin Vigouroux, Michal Syonov, Yuriy Baglaenko, Angeliki M Nikolakopoulou, Dene Ringuette, Horea Rus, Peter V DiStefano, Suzie Dufour, Alireza P Shabanzadeh and 11 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2024. 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
0.7field-weighted citation impact, top 31% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
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

21 authors at 6 institutions in 4 countries.

Xue Fan Wang *Krembil Research Institute, University Health Network, Krembil Discovery Tower, 60 Leonard St.,, Toronto, M5T 2O8, ON, Canada.
Robin Vigouroux *Krembil Research Institute, University Health Network, Krembil Discovery Tower, 60 Leonard St.,, Toronto, M5T 2O8, ON, Canada.ORCID 0000-0002-3217-895X
Michal Syonov *Krembil Research Institute, University Health Network, Krembil Discovery Tower, 60 Leonard St.,, Toronto, M5T 2O8, ON, Canada.
Yuriy BaglaenkoKrembil Research Institute, University Health Network, Krembil Discovery Tower, 60 Leonard St.,, Toronto, M5T 2O8, ON, Canada.
Angeliki M NikolakopoulouDepartment of Physiology and Neuroscience, The Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Dene RinguetteKrembil Research Institute, University Health Network, Krembil Discovery Tower, 60 Leonard St.,, Toronto, M5T 2O8, ON, Canada.
Horea RusUniversity of Maryland, School of Medicine, Department of Neurology, Baltimore, MD, 21201, USA.ORCID 0000-0003-2415-5130
Peter V DiStefanoToronto General Hospital Research Institute, University Health Network, 101 College St. Rm 3-308, Toronto, M5L 1L7, ON, Canada.
Suzie DufourKrembil Research Institute, University Health Network, Krembil Discovery Tower, 60 Leonard St.,, Toronto, M5T 2O8, ON, Canada.
Alireza P ShabanzadehKrembil Research Institute, University Health Network, Krembil Discovery Tower, 60 Leonard St.,, Toronto, M5T 2O8, ON, Canada.
Seunggi LeeKrembil Research Institute, University Health Network, Krembil Discovery Tower, 60 Leonard St.,, Toronto, M5T 2O8, ON, Canada.
Bernhard K MuellerBioNTech resano GmbH, An der Goldgrube 12,, 55131, Mainz, Germany.
Jason CharishKrembil Research Institute, University Health Network, Krembil Discovery Tower, 60 Leonard St.,, Toronto, M5T 2O8, ON, Canada.
Hidekiyo HaradaKrembil Research Institute, University Health Network, Krembil Discovery Tower, 60 Leonard St.,, Toronto, M5T 2O8, ON, Canada.ORCID 0000-0001-6758-4141
Jason E FishToronto General Hospital Research Institute, University Health Network, 101 College St. Rm 3-308, Toronto, M5L 1L7, ON, Canada.ORCID 0000-0003-0640-7277
Joan WitherKrembil Research Institute, University Health Network, Krembil Discovery Tower, 60 Leonard St.,, Toronto, M5T 2O8, ON, Canada.
Thomas WälchliKrembil Research Institute, University Health Network, Krembil Discovery Tower, 60 Leonard St.,, Toronto, M5T 2O8, ON, Canada.ORCID 0000-0002-8961-6551
Jean-François CloutierThe Neuro - Montreal Neurological Institute and Hospital, 3801 Rue Université, Montréal, QC, H3A 2B4, Canada.ORCID 0000-0003-0840-2795
Berislav V ZlokovicDepartment of Physiology and Neuroscience, The Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.ORCID 0000-0002-6802-8232
Peter L CarlenKrembil Research Institute, University Health Network, Krembil Discovery Tower, 60 Leonard St.,, Toronto, M5T 2O8, ON, Canada.ORCID 0000-0002-3339-8102
Philippe P MonnierKrembil Research Institute, University Health Network, Krembil Discovery Tower, 60 Leonard St.,, Toronto, M5T 2O8, ON, Canada. Philippe.Monnier@uhn.ca.ORCID 0000-0002-6221-4130
University Health Network · CAUniversity of New Brunswick · CAUniversity of Southern California · USBioNTech (Germany) · DEMontreal Neurological Institute and Hospital · CAUniversity of Maryland, Baltimore · US

Funding

Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) PJT 162094Heart and Stroke Foundation of Canada (Heart and Stroke Foundation) NA7067
6 · The paper itself

Abstract

Liver failure causes breakdown of the Blood CNS Barrier (BCB) leading to damages of the Central-Nervous-System (CNS), however the mechanisms whereby the liver influences BCB-integrity remain elusive. One possibility is that the liver secretes an as-yet to be identified molecule(s) that circulate in the serum to directly promote BCB-integrity. To study BCB-integrity, we developed light-sheet imaging for three-dimensional analysis. We show that liver- or muscle-specific knockout of Hfe2/Rgmc induces BCB-breakdown, leading to accumulation of toxic-blood-derived fibrinogen in the brain, lower cortical neuron numbers, and behavioral deficits in mice. Soluble HFE2 competes with its homologue RGMa for binding to Neogenin, thereby blocking RGMa-induced downregulation of PDGF-B and Claudin-5 in endothelial cells, triggering BCB-disruption. HFE2 administration in female mice with experimental autoimmune encephalomyelitis, a model for multiple sclerosis, prevented paralysis and immune cell infiltration by inhibiting RGMa-mediated BCB alteration. This study has implications for the pathogenesis and potential treatment of diseases associated with BCB-dysfunction.

Indexed as

Blood-Brain BarrierEncephalomyelitis, Autoimmune, ExperimentalAnimalsCentral Nervous SystemEndothelial CellsFemaleGPI-Linked ProteinsHemochromatosis ProteinLiverMiceMusclesGPI-Linked ProteinsHemochromatosis ProteinHJV protein, mouse

Identifiers

PMID38310100
PMCPMC10838306
OpenAlexW4391509730

What OpenQuestion 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 OpenQuestion graph.