The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.
Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage
Open accessAbstract
Summary 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 homologue 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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Metadata
- Authors
- Petersen, M. A., Ryu, J. K., Chang, K.-J., Etxeberria, A., Bardehle, S., Mendiola, A. S., Kamau-Devers, W., Fancy, S. P. J., Thor, A., Bushong, E. A., Baeza-Raja, B., Syme, C. A., Wu, M. D., Rios Coronado, P. E., Meyer-Franke, A., Yahn, S., Pous, L., Lee, J. K., Schachtrup, C., Lassmann, H., Huang, E. J., Han, M. H., Absinta, M., Reich, D. S., Ellisman, M. H., Rowitch, D. H., Chan, J. R., & Akassoglou, K.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 96
- Issue
- 5
- Pages
- 1003-1012.e7
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2766876983
- Cited by
- 201
- References
- 17
- FWCI
- 10.76
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Petersen, M. A., Ryu, J. K., Chang, K.-J., Etxeberria, A., Bardehle, S., Mendiola, A. S., Kamau-Devers, W., Fancy, S. P. J., Thor, A., Bushong, E. A., Baeza-Raja, B., Syme, C. A., Wu, M. D., Rios Coronado, P. E., Meyer-Franke, A., Yahn, S., Pous, L., Lee, J. K., Schachtrup, C., . . . Akassoglou, K. (2017). Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage. Neuron. https://doi.org/10.1016/j.neuron.2017.10.008
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
