ArticleNeuron2017
Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage.
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Article in Neuron, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 1 of them a synthesis that pooled it.
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118citing papers in PubMed, 1 pooled it
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Who cites it
118 citing papers in PubMed, 1 synthesis or guideline pooled it, 203 citations in OpenAlex.
- Current status of neuroprotective and neuroregenerative strategies in multiple sclerosis: A systematic review.Multiple sclerosis (Houndmills, Basingstoke, England) · 2022Pooled it
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- ID3 -depleted human induced pluripotent stem cell-derived neural stem/progenitor cells promote neurorepair.Neural regeneration research · 2026Article
- Beyond the barrier: Targeting blood-brain interactions for neuroprotection and repair.Neural regeneration research · 2026Article
- CRP Deficiency Rescues Periodontitis-Induced Hippocampal Neurogenesis Impairment by Suppressing OPC-Derived BMP4 Signaling in Rats.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hypoxia or tobacco-smoke exposure induce region-specific microvascular remodeling in the brain.Scientific reports · 2026Article
- Routes of precursors' migration in remyelination.Brain : a journal of neurology · 2026Review
- Age and Maturation Stage Linked Consequences of Fibrinogen on Human Oligodendroglia.Journal of neuroscience research · 2026Article
- The role of ECM-PIEZO1-axis-mediated mechanosensation in the central nervous system.Frontiers in neurology · 2026Review
- Glymphatic dysfunction and cognitive impairment in tuberculous meningitis: insights from diffusion tensor imaging along the perivascular space (DTI-ALPS).Frontiers in neuroscience · 2026Article
- Post-ischemic modification of neurogenesis and oligodendrogenesis in rodent models.Frontiers in neural circuits · 2026Review
- Development of a humanized anti-fibrin monoclonal antibody for the treatment of neuroinflammatory and retinal diseases.Journal of neuroinflammation · 2025Article
- Pathological mechanisms of motor dysfunction in familial Danish dementia: insights from a knock-in rat model.Journal of neuroinflammation · 2025Article
- Inhibition of astrocyte BMP signaling alleviates neuroinflammation in experimental models of Parkinson's disease.Cell death discovery · 2025Article
- Extending the Branches of Neonatal Neurocritical Care.Seminars in perinatology · 2025Review
- SnRNA-seq Interprets Mechanisms by which Three Glial Cell Types Influence Myelin Regeneration in Adult Drug-Resistant Epilepsy-Related Cognitive Impairment.Molecular neurobiology · 2025Article
- Spatially-restricted inflammation-induced senescent-like glia in multiple sclerosis and patient-derived organoids.Nature communications · 2025Article
- Transcriptomic and histological characteristics of innate immune activation in brain parenchyma in a rat model of neonatal intraventricular hemorrhage.Fluids and barriers of the CNS · 2025Article
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- Endothelial PD-1 Regulates Vascular Homeostasis and Oligodendrogenesis during Brain Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
58 more citing papers are in PubMed but not listed here.
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Authors and funding
28 authors at 10 institutions in 4 countries.
Mark A PetersenGladstone Institutes, San Francisco, CA, USA; Department of Pediatrics, University of California, San Francisco, CA, USA.
Jae Kyu RyuGladstone Institutes, San Francisco, CA, USA.
Kae-Jiun ChangDepartment of Neurology, University of California, San Francisco, CA, USA.
Ainhoa EtxeberriaDepartment of Neurology, University of California, San Francisco, CA, USA.
Sophia BardehleGladstone Institutes, San Francisco, CA, USA.
Andrew S MendiolaGladstone Institutes, San Francisco, CA, USA.
Wanjiru Kamau-DeversGladstone Institutes, San Francisco, CA, USA; Berkeley City College, Berkeley, CA, USA.
Stephen P J FancyDepartment of Pediatrics, University of California, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, CA, USA; Newborn Brain Research Institute, University of California, San Francisco, CA, USA.
Andrea ThorNational Center for Microscopy and Imaging Research, Center for Research in Biological Systems, University of California, San Diego, La Jolla, CA, USA.
Eric A BushongNational Center for Microscopy and Imaging Research, Center for Research in Biological Systems, University of California, San Diego, La Jolla, CA, USA.
Bernat Baeza-RajaGladstone Institutes, San Francisco, CA, USA.
Catriona A SymeGladstone Institutes, San Francisco, CA, USA.
Michael D WuGladstone Institutes, San Francisco, CA, USA; Department of Anesthesia, University of California, San Francisco, CA, USA.
Pamela E Rios CoronadoGladstone Institutes, San Francisco, CA, USA.
Anke Meyer-FrankeGladstone Institutes, San Francisco, CA, USA.
Stephanie YahnMiami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.
Lauriane PousFaculty of Biology, University of Freiburg, Freiburg, Germany.
Jae K LeeMiami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.
Christian SchachtrupInstitute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Hans LassmannCenter for Brain Research, Medical University of Vienna, Vienna, Austria.
Eric J HuangDepartment of Pathology, University of California, San Francisco, CA, USA.
May H HanDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Martina AbsintaTranslational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Daniel S ReichTranslational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Mark H EllismanNational Center for Microscopy and Imaging Research, Center for Research in Biological Systems, University of California, San Diego, La Jolla, CA, USA; Department of Neurosciences, University of California, San Diego, La Jolla, California, USA; Salk Institute for Biological Studies, La Jolla, San Diego, California, USA.
David H RowitchDepartment of Pediatrics, University of California, San Francisco, CA, USA; Department of Neurosurgery, Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, CA, USA; Department of Paediatrics, University of Cambridge, Cambridge, UK.
Jonah R ChanDepartment of Neurology, University of California, San Francisco, CA, USA.
Katerina AkassoglouGladstone Institutes, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, CA, USA. Electronic address: kakassoglou@gladstone.ucsf.edu.
Gladstone Institutes · USUniversity of California, San Francisco · USUniversity of California, San Diego · USUniversity of Freiburg · DEUniversity of Miami · USMedical University of Vienna · ATNational Institute of Neurological Disorders and Stroke · USNational Institutes of Health · USSalk Institute for Biological Studies · USStanford University · US
Funding
Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVEN Grant DEEKS · 1988 to 2026
$93.6MMultimodal MRI in Multiple SclerosisZIANS003119 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI REICH, DANIEL · 2010 to 2025
$53.4MPediatric Scientist Development Program (PSDP) [K12]K12HD000850 · NICHD · YALE UNIVERSITY · PI Sallie R. Permar · 1987 to 2026
$44.1MIVEM and Image Analysis ResourceP41GM103412 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ELLISMAN, MARK H · 2012 to 2019
$17.9MRegulation of Cellular Pathwaysin Human Brain DevelopmentP01NS083513 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FANCY, STEPHEN PHILIP JAMES · 2014 to 2024
$12.6MNeurovascular Interactions: Mechanisms, imaging, therapeutic potentialR35NS097976 · NINDS · J. DAVID GLADSTONE INSTITUTES · PI AKASSOGLOU, KATERINA · 2016 to 2023
$11.1MNew Probe and Methods for Correlated LM & EMR01GM086197 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ADAMS, STEPHEN ROY, BOASSA, DANIELA · 2008 to 2020
$8.3MDYNAMICS OF SIGNAL TRANSDUCTION IN NEURONSR01NS027177 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ADAMS, STEPHEN ROY, ELLISMAN, MARK H · 1989 to 2017
$5.8MTHE ESTABLISHMENT OF SCHWANN CELL POLARITY AND THE INITIATION OF MYELINATIONR01NS062796 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHAN, JONAH R · 2008 to 2018
$3.4MEXTRAMULAR RESEARCH FACILITIES CONSTRUCTIONC06RR018928 · NCRR · J. DAVID GLADSTONE INSTITUTES · PI MAHLEY, ROBERT W. · 2003 to 2003
$2.1MChild Health Career Development Program at UCSFK12HD072222 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIERO, DONNA M. · 2013 to 2017
$2.0MFunctional Screening of GPCR Small Molecule Libraries for Remyelination TherapiesR01NS095889 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHAN, JONAH R · 2016 to 2020
$1.9MMedical Research Council MC_PC_12009NCRR NIH HHS C06 RR018928NCRR NIH HHS S10 RR028962NIAID NIH HHS P30 AI027763NICHD NIH HHS K12 HD000850NICHD NIH HHS K12 HD072222NIGMS NIH HHS P41 GM103412NIGMS NIH HHS R01 GM086197NINDS NIH HHS P01 NS083513NINDS NIH HHS R01 NS027177NINDS NIH HHS R01 NS062796NINDS NIH HHS R01 NS095889NINDS NIH HHS R01 NS097551NINDS NIH HHS R35 NS097976
Abstract
Blood-brain barrier (BBB) disruption alters the composition of the brain microenvironment by allowing blood proteins into the CNS. However, whether blood-derived molecules serve as extrinsic inhibitors of remyelination is unknown. Here we show that the coagulation factor fibrinogen activates the bone morphogenetic protein (BMP) signaling pathway in oligodendrocyte progenitor cells (OPCs) and suppresses remyelination. Fibrinogen induces phosphorylation of Smad 1/5/8 and inhibits OPC differentiation into myelinating oligodendrocytes (OLs) while promoting an astrocytic fate in vitro. Fibrinogen effects are rescued by BMP type I receptor inhibition using dorsomorphin homolog 1 (DMH1) or CRISPR/Cas9 activin A receptor type I (ACVR1) knockout in OPCs. Fibrinogen and the BMP target Id2 are increased in demyelinated multiple sclerosis (MS) lesions. Therapeutic depletion of fibrinogen decreases BMP signaling and enhances remyelination in vivo. Targeting fibrinogen may be an upstream therapeutic strategy to promote the regenerative potential of CNS progenitors in diseases with remyelination failure.
Indexed as
Activin Receptors, Type IAnimalsBlood VesselsBone Morphogenetic ProteinsFibrinogenLysophosphatidylcholinesMiceMice, Inbred C57BLMice, KnockoutMicroarray AnalysisMyelin SheathOligodendrocyte Precursor CellsPlasmidsRemyelinationSignal TransductionActivin Receptors, Type IAcvr1 protein, mouseBone Morphogenetic ProteinsFibrinogenLysophosphatidylcholinesancrodcell fatefibrinmyelinneonatal brain injuryneuroinflammationNG2 cellsregenerationstem/progenitor cellsvasculature
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