Vitronectin mitigates stroke-increased neurogenesis only in female mice and through FAK-regulated IL-6.
Astrocyte
Cytokines
Focal adhesion kinase
Ischemic stroke
Neurogenesis
Vitronectin
Journal
Experimental neurology
ISSN: 1090-2430
Titre abrégé: Exp Neurol
Pays: United States
ID NLM: 0370712
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
05
09
2019
revised:
03
10
2019
accepted:
20
10
2019
pubmed:
5
11
2019
medline:
22
7
2020
entrez:
4
11
2019
Statut:
ppublish
Résumé
Vitronectin (VTN) is a blood protein produced mainly by the liver. We show that VTN leaks from the bloodstream into the injury site and neighboring subventricular zone (SVZ) following ischemic stroke (middle cerebral artery occlusion, MCAO) in adult mice. MCAO is known to increase neurogenesis after stroke. VTN inhibits this response in females, but not in males, as shown by ~70% more stroke-induced SVZ neurogenesis in female VTN-/- mice at 14 d. In female VTN-/- mice, stroke-induced expression of interleukin-6 (IL-6) at 24 h was reduced in the SVZ. The closely related leukemia inhibitory factor (LIF) or pro-neurogenic ciliary neurotrophic factor (CNTF) were not affected. The female-specific effect of VTN on IL-6 expression was not due to sex hormones, as shown by ovariectomy and castration. IL-6 injection next to the SVZ reversed the MCAO-induced increase in neurogenesis seen in VTN-/- mice. Our in vitro and vivo data suggest that plasma VTN activates focal adhesion kinase (FAK) in the SVZ following MCAO, which reduces IL-6 expression in astrocytes but increases it in other cells such as microglia/macrophages. Inducible conditional astrocytic FAK deletion increased MCAO-induced IL-6 expression in females at 24 h and blocked MCAO-induced neurogenesis at 14 d, confirming a key detrimental role of IL-6. Collectively, these data suggest that leakage of VTN into the SVZ reduces the neurogenic response to stroke in female mice by promoting IL-6 expression. Reducing VTN or VTN signaling may be an approach to promote neurogenesis for neuroprotection and cell replacement after stroke in females.
Identifiants
pubmed: 31678139
pii: S0014-4886(19)30235-3
doi: 10.1016/j.expneurol.2019.113088
pmc: PMC6901344
mid: NIHMS1542965
pii:
doi:
Substances chimiques
Interleukin-6
0
Vitronectin
0
interleukin-6, mouse
0
Focal Adhesion Kinase 1
EC 2.7.10.2
Ptk2 protein, mouse
EC 2.7.10.2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
113088Subventions
Organisme : NCRR NIH HHS
ID : C06 RR030651
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG029493
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
Références
J Cereb Blood Flow Metab. 2017 Mar;37(3):1030-1045
pubmed: 27174996
Cell Death Differ. 2016 Sep 1;23(9):1515-28
pubmed: 27104929
Cell Rep. 2019 Jan 8;26(2):394-406.e5
pubmed: 30625322
J Neurosci. 2002 Jan 15;22(2):486-92
pubmed: 11784794
Acta Physiol (Oxf). 2010 Jan;198(1):1-13
pubmed: 19723026
Mol Cell Neurosci. 2003 Jun;23(2):292-301
pubmed: 12812760
Stem Cells. 2019 Mar;37(3):395-406
pubmed: 30431198
J Neurosci. 2006 Nov 15;26(46):12089-99
pubmed: 17108182
Exp Neurol. 2003 Oct;183(2):298-310
pubmed: 14552871
Stem Cell Reports. 2018 May 8;10(5):1464-1480
pubmed: 29628394
Physiol Rev. 2018 Jan 1;98(1):239-389
pubmed: 29351512
Neurobiol Dis. 2018 Jul;115:49-58
pubmed: 29605425
J Cereb Blood Flow Metab. 2008 Sep;28(9):1574-87
pubmed: 18493257
J Neurosci. 2012 Jul 4;32(27):9277-87
pubmed: 22764235
Mol Cell Neurosci. 2004 Nov;27(3):255-66
pubmed: 15519241
J Neurosci. 2008 Feb 27;28(9):2231-41
pubmed: 18305256
Neuroscientist. 2008 Aug;14(4):369-80
pubmed: 18024854
Glia. 2018 Nov;66(11):2456-2469
pubmed: 30500112
Exp Neurol. 1997 Sep;147(1):1-9
pubmed: 9294397
J Cereb Blood Flow Metab. 2009 Mar;29(3):464-79
pubmed: 19018268
J Cereb Blood Flow Metab. 2009 Oct;29(10):1644-54
pubmed: 19536070
Sci Rep. 2016 Oct 11;6:35108
pubmed: 27725773
Psychoneuroendocrinology. 2019 Feb;100:96-105
pubmed: 30299260
Ann Neurol. 2011 Oct;70(4):616-26
pubmed: 21710624
Neuroscience. 2007 Mar 16;145(2):470-83
pubmed: 17241745
Transl Stroke Res. 2014 Apr;5(2):301-11
pubmed: 24323721
J Cereb Blood Flow Metab. 2012 Sep;32(9):1677-98
pubmed: 22739623
Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10061-5
pubmed: 7694279
J Cell Sci. 2006 Oct 1;119(Pt 19):3901-3
pubmed: 16988024
Nat Biotechnol. 2002 Nov;20(11):1103-10
pubmed: 12379867
Brain Sci. 2016 May 17;6(2):
pubmed: 27196935
Science. 1999 Aug 13;285(5430):1028-32
pubmed: 10446041
J Cell Sci. 2018 Feb 2;131(3):
pubmed: 29222114
J Cereb Blood Flow Metab. 2002 Sep;22(9):1068-79
pubmed: 12218412
Neurobiol Aging. 2015 Feb;36(2):1045-56
pubmed: 25482245
PLoS One. 2011;6(10):e25863
pubmed: 22031820
J Immunol. 2007 Jun 15;178(12):8158-67
pubmed: 17548654
Exp Neurol. 2015 Jul;269:75-89
pubmed: 25819103
J Comp Neurol. 2007 Feb 20;500(6):1064-75
pubmed: 17183542
Neurobiol Dis. 2010 Feb;37(2):267-74
pubmed: 19909815
J Neurosci Res. 2005 Apr 15;80(2):160-71
pubmed: 15751027
Prog Neurobiol. 2016 Sep;144:103-20
pubmed: 26455456
Science. 2003 Dec 5;302(5651):1760-5
pubmed: 14615545
Development. 2005 Feb;132(3):565-78
pubmed: 15634701
Clin Dev Immunol. 2013;2013:746068
pubmed: 24223607
J Comp Neurol. 2005 Jul 25;488(2):201-14
pubmed: 15924343
Int J Biol Sci. 2012;8(9):1254-66
pubmed: 23136554
J Neurosci. 2006 Jan 25;26(4):1269-74
pubmed: 16436614
J Neuroimmunol. 1999 Dec;100(1-2):124-39
pubmed: 10695723
J Cereb Blood Flow Metab. 2016 Dec;36(12):2034-2043
pubmed: 27742890
Stroke. 2007 Feb;38(2 Suppl):646-51
pubmed: 17261708
PLoS One. 2012;7(7):e40843
pubmed: 22815838
Exp Neurol. 2011 Jun;229(2):391-8
pubmed: 21419118
Nat Rev Neurosci. 2007 Mar;8(3):221-32
pubmed: 17311007
J Cereb Blood Flow Metab. 2006 Jan;26(1):1-20
pubmed: 15959458
Glia. 2013 Feb;61(2):192-209
pubmed: 23027402
Neurobiol Dis. 2013 Jan;49:68-78
pubmed: 22960105
Eur J Neurosci. 2006 Jul;24(1):45-54
pubmed: 16882007
Neuroreport. 2011 Feb 16;22(3):126-30
pubmed: 21266900
Glia. 2009 Jun;57(8):835-49
pubmed: 19053043
Neuroscience. 2015 Oct 29;307:160-70
pubmed: 26327363
Ann Neurol. 2002 Dec;52(6):802-13
pubmed: 12447935
Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13632-7
pubmed: 14581618
J Neurosci. 2001 Oct 1;21(19):7642-53
pubmed: 11567054
Nat Med. 2002 Sep;8(9):963-70
pubmed: 12161747
J Neurosci Res. 2009 Nov 15;87(15):3297-305
pubmed: 19025772
J Neurosci Res. 2005 Dec 1;82(5):701-16
pubmed: 16267827
Neurochem Int. 2007 Jun;50(7-8):1028-41
pubmed: 17531349
Exp Neurol. 2019 Feb;312:20-32
pubmed: 30408465
Neurobiol Dis. 2015 Feb;74:229-39
pubmed: 25484283
Hippocampus. 2004;14(7):861-75
pubmed: 15382256
J Cereb Blood Flow Metab. 2012 May;32(5):919-32
pubmed: 22354151
J Neurosci. 2006 Dec 13;26(50):13007-16
pubmed: 17167090