Examinando por Autor "Rojas-Mancilla, Edgardo"

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    αVβ3 Integrin regulates astrocyte reactivity
    (Journal, 2017-09) 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
    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. © 2017 The Author(s).