alpha (V) beta (3) Integrin regulates astrocyte reactivity
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2017Metadata
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Lagos Cabre, Raúl
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alpha (V) beta (3) Integrin regulates astrocyte reactivity
Author
- Lagos Cabre, Raúl;
- Álvarez, Álvaro;
- Kong, Milene;
- Burgos Bravo, Francesca;
- Cárdenas, Areli;
- Rojas Mancilla, Edgardo;
- Pérez Núñez, Ramón Daniel;
- Herrera Molina, Rodrigo;
- Rojas, Fabiola;
- Schneider, Pascal;
- Herrera-Marschitz Muller, Mario;
- Quest, Andrew F. G.;
- van Zundert, Brigitte;
- Leyton Campos, Lisette;
Abstract
Background: Neuroinflammation involves cytokine release, astrocyte reactivity and migration. Neuronal Thy-1 promotes DITNC1 astrocyte migration by engaging alpha(V)beta(3) Integrin and Syndecan-4. Primary astrocytes express low levels of these receptors and are unresponsive to Thy-1; thus, inflammation and astrocyte reactivity might be necessary for Thy-1-induced responses.
Methods: Wild-type rat astrocytes (TNF-activated) or from human SOD1(G93A) transgenic mice (a neurodegenerative disease model) were used to evaluate cell migration, Thy-1 receptor levels, signaling molecules, and reactivity markers.
Results: Thy-1 induced astrocyte migration only after TNF priming. Increased expression of alpha(V)beta(3) Integrin, Syndecan-4, P2X7R, Pannexin-1, Connexin-43, GFAP, and iNOS were observed in TNF-treated astrocytes. Silencing of beta(3) Integrin prior to TNF treatment prevented Thy-1-induced migration, while beta(3) Integrin over-expression was sufficient to induce astrocyte reactivity and allow Thy-1-induced migration. Finally, hSOD1(G93A) astrocytes behave as TNF-treated astrocytes since they were reactive and responsive to Thy-1.
Conclusions: Therefore, inflammation induces expression of alpha(V)beta(3) Integrin and other proteins, astrocyte reactivity, and Thy-1 responsiveness. Importantly, ectopic control of beta(3) Integrin levels modulates these responses regardless of inflammation.
Patrocinador
FONDECYT
3140460
1150744
1130250
1170925
1140301
3140471
3170645
CONICYT
21090323
21130008
CONICYT-FONDAP
15130011
Swiss National Science Foundation
310030_156961
Anillo
ACT-1114
DRI USA
2013-0030
ATA
2014-F-034
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Artículo de publicación ISI
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Journal of Neuroinflammation (2017) 14:194
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