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Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage.
Petersen, Mark A; Ryu, Jae Kyu; Chang, Kae-Jiun; Etxeberria, Ainhoa; Bardehle, Sophia; Mendiola, Andrew S; Kamau-Devers, Wanjiru; Fancy, Stephen P J; Thor, Andrea; Bushong, Eric A; Baeza-Raja, Bernat; Syme, Catriona A; Wu, Michael D; Rios Coronado, Pamela E; Meyer-Franke, Anke; Yahn, Stephanie; Pous, Lauriane; Lee, Jae K; Schachtrup, Christian; Lassmann, Hans; Huang, Eric J; Han, May H; Absinta, Martina; Reich, Daniel S; Ellisman, Mark H; Rowitch, David H; Chan, Jonah R; Akassoglou, Katerina.
Afiliación
  • Petersen MA; Gladstone Institutes, San Francisco, CA, USA; Department of Pediatrics, University of California, San Francisco, CA, USA.
  • Ryu JK; Gladstone Institutes, San Francisco, CA, USA.
  • Chang KJ; Department of Neurology, University of California, San Francisco, CA, USA.
  • Etxeberria A; Department of Neurology, University of California, San Francisco, CA, USA.
  • Bardehle S; Gladstone Institutes, San Francisco, CA, USA.
  • Mendiola AS; Gladstone Institutes, San Francisco, CA, USA.
  • Kamau-Devers W; Gladstone Institutes, San Francisco, CA, USA; Berkeley City College, Berkeley, CA, USA.
  • Fancy SPJ; Department 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.
  • Thor A; National Center for Microscopy and Imaging Research, Center for Research in Biological Systems, University of California, San Diego, La Jolla, CA, USA.
  • Bushong EA; National Center for Microscopy and Imaging Research, Center for Research in Biological Systems, University of California, San Diego, La Jolla, CA, USA.
  • Baeza-Raja B; Gladstone Institutes, San Francisco, CA, USA.
  • Syme CA; Gladstone Institutes, San Francisco, CA, USA.
  • Wu MD; Gladstone Institutes, San Francisco, CA, USA; Department of Anesthesia, University of California, San Francisco, CA, USA.
  • Rios Coronado PE; Gladstone Institutes, San Francisco, CA, USA.
  • Meyer-Franke A; Gladstone Institutes, San Francisco, CA, USA.
  • Yahn S; Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.
  • Pous L; Faculty of Biology, University of Freiburg, Freiburg, Germany.
  • Lee JK; Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.
  • Schachtrup C; Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Lassmann H; Center for Brain Research, Medical University of Vienna, Vienna, Austria.
  • Huang EJ; Department of Pathology, University of California, San Francisco, CA, USA.
  • Han MH; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
  • Absinta M; Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
  • Reich DS; Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
  • Ellisman MH; National 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 Di
  • Rowitch DH; Department 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
  • Chan JR; Department of Neurology, University of California, San Francisco, CA, USA.
  • Akassoglou K; Gladstone Institutes, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, CA, USA. Electronic address: kakassoglou@gladstone.ucsf.edu.
Neuron ; 96(5): 1003-1012.e7, 2017 Dec 06.
Article en En | MEDLINE | ID: mdl-29103804
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fibrinógeno / Proteínas Morfogenéticas Óseas / Células Precursoras de Oligodendrocitos / Remielinización Límite: Animals Idioma: En Revista: Neuron Asunto de la revista: NEUROLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fibrinógeno / Proteínas Morfogenéticas Óseas / Células Precursoras de Oligodendrocitos / Remielinización Límite: Animals Idioma: En Revista: Neuron Asunto de la revista: NEUROLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA