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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2017

Open Access 01-12-2017 | Research

αVβ3 Integrin regulates astrocyte reactivity

Authors: Raúl Lagos-Cabré, Alvaro Alvarez, Milene Kong, Francesca Burgos-Bravo, Areli Cárdenas, Edgardo Rojas-Mancilla, Ramón Pérez-Nuñez, Rodrigo Herrera-Molina, Fabiola Rojas, Pascal Schneider, Mario Herrera-Marschitz, Andrew F. G. Quest, Brigitte van Zundert, Lisette Leyton

Published in: Journal of Neuroinflammation | Issue 1/2017

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Abstract

Background

Neuroinflammation involves cytokine release, astrocyte reactivity and migration. Neuronal Thy-1 promotes DITNC1 astrocyte migration by engaging αVβ3 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 SOD1G93A 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 αVβ3 Integrin, Syndecan-4, P2X7R, Pannexin-1, Connexin-43, GFAP, and iNOS were observed in TNF-treated astrocytes. Silencing of β3 Integrin prior to TNF treatment prevented Thy-1-induced migration, while β3 Integrin over-expression was sufficient to induce astrocyte reactivity and allow Thy-1-induced migration. Finally, hSOD1G93A astrocytes behave as TNF-treated astrocytes since they were reactive and responsive to Thy-1.

Conclusions

Therefore, inflammation induces expression of αVβ3 Integrin and other proteins, astrocyte reactivity, and Thy-1 responsiveness. Importantly, ectopic control of β3 Integrin levels modulates these responses regardless of inflammation.
Appendix
Available only for authorised users
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Metadata
Title
αVβ3 Integrin regulates astrocyte reactivity
Authors
Raúl Lagos-Cabré
Alvaro Alvarez
Milene Kong
Francesca Burgos-Bravo
Areli Cárdenas
Edgardo Rojas-Mancilla
Ramón Pérez-Nuñez
Rodrigo Herrera-Molina
Fabiola Rojas
Pascal Schneider
Mario Herrera-Marschitz
Andrew F. G. Quest
Brigitte van Zundert
Lisette Leyton
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2017
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-017-0968-5

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