Vitronectin from brain pericytes promotes adult forebrain neurogenesis by stimulating CNTF.
Animals
Antibodies
/ administration & dosage
Brain
/ drug effects
Ciliary Neurotrophic Factor
/ biosynthesis
Humans
Injections, Intraventricular
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neurogenesis
/ drug effects
Pericytes
/ drug effects
Prosencephalon
/ drug effects
Vitronectin
/ antagonists & inhibitors
Astrocyte
Cytokines
Focal adhesion kinase
Neurogenesis
Vitronectin
gp130 signaling
Journal
Experimental neurology
ISSN: 1090-2430
Titre abrégé: Exp Neurol
Pays: United States
ID NLM: 0370712
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
29
05
2018
revised:
17
09
2018
accepted:
05
11
2018
pubmed:
9
11
2018
medline:
2
5
2019
entrez:
9
11
2018
Statut:
ppublish
Résumé
Vitronectin (VTN) is a glycoprotein in the blood and affects hemostasis. VTN is also present in the extracellular matrix of various organs but little is known about its function in healthy adult tissues. We show, in adult mice, that VTN is uniquely expressed by approximately half of the pericytes of subventricular zone (SVZ) where neurogenesis continues throughout life. Intracerebral VTN antibody injection or VTN knockout reduced neurogenesis as well as expression of pro-neurogenic CNTF, and anti-neurogenic LIF and IL-6. Conversely, injections of VTN, or plasma from VTN+/+, but not VTN-/- mice, increased these cytokines. VTN promoted SVZ neurogenesis when LIF and IL-6 were suppressed by co-administration of a gp130 inhibitor. Unexpectedly, VTN inhibited FAK signaling and VTN-/- mice had increased FAK signaling in the SVZ. Further, an FAK inhibitor or VTN increased CNTF expression, but not in conditional astrocytic FAK knockout mice, suggesting that VTN increases CNTF through FAK inhibition in astrocytes. These results identify a novel role of pericyte-derived VTN in the brain, where it regulates SVZ neurogenesis through co-expression of CNTF, LIF and IL-6. VTN-integrin-FAK and gp130 signaling may provide novel targets to induce neurogenesis for cell replacement therapies.
Identifiants
pubmed: 30408465
pii: S0014-4886(18)30660-5
doi: 10.1016/j.expneurol.2018.11.002
pmc: PMC6326873
mid: NIHMS1512364
pii:
doi:
Substances chimiques
Antibodies
0
Ciliary Neurotrophic Factor
0
Vitronectin
0
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
20-32Subventions
Organisme : NCRR NIH HHS
ID : C06 RR030651
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG029493
Pays : United States
Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.
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