Oncostatin M-induced astrocytic tissue inhibitor of metalloproteinases-1 drives remyelination.
Animals
Astrocytes
/ metabolism
Axons
Central Nervous System
/ metabolism
Demyelinating Diseases
/ metabolism
Humans
Interleukin-6
/ metabolism
Mice
Mice, Knockout
Multiple Sclerosis
/ metabolism
Myelin Sheath
Oligodendrocyte Precursor Cells
Oncostatin M
/ metabolism
Remyelination
/ physiology
Tissue Inhibitor of Metalloproteinase-1
/ genetics
astrocytes
oligodendrocyte precursor cells
oncostatin M
remyelination
tissue inhibitor of metalloproteinases-1
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
03 03 2020
03 03 2020
Historique:
pubmed:
20
2
2020
medline:
1
7
2020
entrez:
20
2
2020
Statut:
ppublish
Résumé
The brain's endogenous capacity to restore damaged myelin deteriorates during the course of demyelinating disorders. Currently, no treatment options are available to establish remyelination. Chronic demyelination leads to damaged axons and irreversible destruction of the central nervous system (CNS). We identified two promising therapeutic candidates which enhance remyelination: oncostatin M (OSM), a member of the interleukin-6 family, and downstream mediator tissue inhibitor of metalloproteinases-1 (TIMP-1). While remyelination was completely abrogated in OSMRβ knockout (KO) mice, OSM overexpression in the chronically demyelinated CNS established remyelination. Astrocytic TIMP-1 was demonstrated to play a pivotal role in OSM-mediated remyelination. Astrocyte-derived TIMP-1 drove differentiation of oligodendrocyte precursor cells into mature oligodendrocytes in vitro. In vivo, TIMP-1 deficiency completely abolished spontaneous remyelination, phenocopying OSMRβ KO mice. Finally, TIMP-1 was expressed by human astrocytes in demyelinated multiple sclerosis lesions, confirming the human value of our findings. Taken together, OSM and its downstream mediator TIMP-1 have the therapeutic potential to boost remyelination in demyelinating disorders.
Identifiants
pubmed: 32071226
pii: 1912910117
doi: 10.1073/pnas.1912910117
pmc: PMC7060743
doi:
Substances chimiques
Interleukin-6
0
Tissue Inhibitor of Metalloproteinase-1
0
Oncostatin M
106956-32-5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5028-5038Déclaration de conflit d'intérêts
The authors declare no competing interest.
Références
Acta Neuropathol. 2017 Feb;133(2):223-244
pubmed: 27766432
J Neuropathol Exp Neurol. 2006 Aug;65(8):783-93
pubmed: 16896312
J Neurochem. 2010 Sep;114(6):1667-77
pubmed: 20598020
Cell Cycle. 2009 May 1;8(9):1444-50
pubmed: 19342884
Trends Immunol. 2016 Sep;37(9):608-620
pubmed: 27443914
Glia. 2018 Aug;66(8):1625-1643
pubmed: 29600597
Glia. 2015 Jan;63(1):132-41
pubmed: 25103368
Neural Regen Res. 2017 Dec;12(12):1939-1944
pubmed: 29323026
J Neurosci. 2006 Oct 25;26(43):10967-83
pubmed: 17065439
Biomaterials. 2015 Jul;56:78-85
pubmed: 25934281
J Biol Chem. 1994 Feb 25;269(8):6215-22
pubmed: 8119965
Blood. 1997 Jul 1;90(1):165-73
pubmed: 9207450
J Neuropathol Exp Neurol. 2015 Jan;74(1):48-63
pubmed: 25470347
Cytokine Growth Factor Rev. 2004 Oct;15(5):379-91
pubmed: 15450253
Glia. 2015 Feb;63(2):242-56
pubmed: 25156142
Glia. 2002 Apr 15;38(2):126-36
pubmed: 11948806
Clin Exp Immunol. 2002 May;128(2):245-54
pubmed: 11985514
Am J Pathol. 2006 Dec;169(6):2104-16
pubmed: 17148673
J Neurosci Res. 2006 Apr;83(5):763-74
pubmed: 16477612
J Neurosci. 2003 Dec 3;23(35):11127-35
pubmed: 14657171
Genome Biol. 2011 Nov 11;12(11):233
pubmed: 22078297
Brain. 1998 Dec;121 ( Pt 12):2221-8
pubmed: 9874475
Neurochem Res. 2000 Aug;25(8):1113-8
pubmed: 11055749
Mol Neurobiol. 2017 Jan;54(1):608-622
pubmed: 26746670
Mol Pharm. 2011 Feb 7;8(1):143-52
pubmed: 20977190
Cell Death Dis. 2012 Jun 28;3:e332
pubmed: 22739984
Nat Rev Neurol. 2015 Jan;11(1):56-64
pubmed: 25385337
FASEB J. 2006 Nov;20(13):2369-71
pubmed: 17023520
J Neurosci. 2002 Nov 1;22(21):9221-7
pubmed: 12417647
Brain Pathol. 2001 Jan;11(1):107-16
pubmed: 11145196
Science. 1992 Mar 13;255(5050):1434-7
pubmed: 1542794
Nature. 1979 Aug 2;280(5721):395-6
pubmed: 460414
J Neurosci Res. 2011 Jan;89(1):13-21
pubmed: 20857501
J Clin Invest. 2017 Sep 1;127(9):3271-3280
pubmed: 28862639
Glia. 2015 Oct;63(10):1729-37
pubmed: 25921393
Mol Neurobiol. 2019 May;56(5):3380-3392
pubmed: 30121936
Nat Rev Neurosci. 2008 Nov;9(11):839-55
pubmed: 18931697
Mol Ther. 2010 Apr;18(4):684-91
pubmed: 20068552
J Neuropathol Exp Neurol. 2001 Nov;60(11):1087-98
pubmed: 11706938
Brain. 1997 Jan;120 ( Pt 1):27-37
pubmed: 9055795
Lancet Neurol. 2015 Feb;14(2):183-93
pubmed: 25772897
J Neuropathol Exp Neurol. 2011 Sep;70(9):758-69
pubmed: 21865884
Glia. 2009 Jun;57(8):807-14
pubmed: 19031445
Brain Sci. 2013 Aug 28;3(3):1282-324
pubmed: 24961530
Nat Med. 2007 Oct;13(10):1228-33
pubmed: 17906634
J Neurosci. 2000 Sep 1;20(17):6404-12
pubmed: 10964946
J Neurosci. 2001 Sep 15;21(18):7046-52
pubmed: 11549714
Nat Med. 2002 Jun;8(6):613-9
pubmed: 12042813
Exp Neurol. 1999 Oct;159(2):333-46
pubmed: 10506506
J Immunol. 2004 Oct 15;173(8):5209-18
pubmed: 15470066
Am J Pathol. 2004 May;164(5):1673-82
pubmed: 15111314
Mol Neurobiol. 2014 Dec;50(3):1142-51
pubmed: 24996996
Neuron. 2006 Mar 16;49(6):823-32
pubmed: 16543131
Nat Cell Biol. 2014 Sep;16(9):889-901
pubmed: 25150980
Haematologica. 2015 Aug;100(8):1005-13
pubmed: 26001794
Am J Pathol. 1998 Mar;152(3):729-41
pubmed: 9502415
Neuroscientist. 2013 Oct;19(5):442-50
pubmed: 23131748
Brain. 2008 Jun;131(Pt 6):1464-77
pubmed: 18490361
Ann Neurol. 2001 Jun;49(6):776-85
pubmed: 11409430
Front Neurosci. 2017 Jan 10;10:613
pubmed: 28119561
J Neurosci. 2011 Apr 20;31(16):6247-54
pubmed: 21508247
J Neurochem. 2013 Oct;127(2):259-70
pubmed: 23647102
Mol Cell Neurosci. 2004 Feb;25(2):252-62
pubmed: 15019942