Peripherally derived FGF21 promotes remyelination in the central nervous system
| Autor: | Morichika Konishi, Noriko Maedera, Mari Yoshida, Nobuyuki Itoh, Yoshihisa Koyama, Rieko Muramatsu, Machika Hamaguchi, Hideki Mochizuki, Toshihide Yamashita, Mariko Kuroda, Harutoshi Fujimura |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Central Nervous System FGF21 Multiple Sclerosis Cellular differentiation Central nervous system Biology Regenerative Medicine Regenerative medicine Permeability 03 medical and health sciences Cuprizone Mice medicine Animals Humans Remyelination Klotho Proteins Myelin Sheath Cell Proliferation Mice Knockout Cell growth Stem Cells Membrane Proteins Cell Differentiation General Medicine In vitro Nerve Regeneration Fibroblast Growth Factors Mice Inbred C57BL Kinetics Oligodendroglia 030104 developmental biology medicine.anatomical_structure Blood-Brain Barrier Immunology Female Pancreas Neuroscience Research Article Demyelinating Diseases |
| Popis: | Demyelination in the central nervous system (CNS) leads to severe neurological deficits that can be partially reversed by spontaneous remyelination. Because the CNS is isolated from the peripheral milieu by the blood-brain barrier, remyelination is thought to be controlled by the CNS microenvironment. However, in this work we found that factors derived from peripheral tissue leak into the CNS after injury and promote remyelination in a murine model of toxin-induced demyelination. Mechanistically, leakage of circulating fibroblast growth factor 21 (FGF21), which is predominantly expressed by the pancreas, drives proliferation of oligodendrocyte precursor cells (OPCs) through interactions with β-klotho, an essential coreceptor of FGF21. We further confirmed that human OPCs expressed β-klotho and proliferated in response to FGF21 in vitro. Vascular barrier disruption is a common feature of many CNS disorders; thus, our findings reveal a potentially important role for the peripheral milieu in promoting CNS regeneration. |
| Databáze: | OpenAIRE |
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