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α(V)β(3) Integrin regulates astrocyte reactivity

BACKGROUND: Neuroinflammation involves cytokine release, astrocyte reactivity and migration. Neuronal Thy-1 promotes DITNC1 astrocyte migration by engaging α(V)β(3) Integrin and Syndecan-4. Primary astrocytes express low levels of these receptors and are unresponsive to Thy-1; thus, inflammation and...

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Detalles Bibliográficos
Autores principales: Lagos-Cabré, Raúl, Alvarez, Alvaro, Kong, Milene, Burgos-Bravo, Francesca, Cárdenas, Areli, Rojas-Mancilla, Edgardo, Pérez-Nuñez, Ramón, Herrera-Molina, Rodrigo, Rojas, Fabiola, Schneider, Pascal, Herrera-Marschitz, Mario, Quest, Andrew F. G., van Zundert, Brigitte, Leyton, Lisette
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622429/
https://www.ncbi.nlm.nih.gov/pubmed/28962574
http://dx.doi.org/10.1186/s12974-017-0968-5
Descripción
Sumario:BACKGROUND: Neuroinflammation involves cytokine release, astrocyte reactivity and migration. Neuronal Thy-1 promotes DITNC1 astrocyte migration by engaging α(V)β(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 α(V)β(3) Integrin, Syndecan-4, P2X7R, Pannexin-1, Connexin-43, GFAP, and iNOS were observed in TNF-treated astrocytes. Silencing of β(3) Integrin prior to TNF treatment prevented Thy-1-induced migration, while β(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 α(V)β(3) Integrin and other proteins, astrocyte reactivity, and Thy-1 responsiveness. Importantly, ectopic control of β(3) Integrin levels modulates these responses regardless of inflammation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-017-0968-5) contains supplementary material, which is available to authorized users.