Journal Article

AlphaVBeta3 Integrin regulates astrocyte reactivity

Alvarez, Alvaro, Burgos-Bravo, Francesca, Herrera-Molina, Rodrigo, Rojas, Fabiola, Quest, Andrew F G, Lagos-Cabre, Raul, Brigitte van Zundert, Rojas-Mancilla, Edgardo, Leyton, Lisette, Perez-Nunez, Ramon, Schneider, Pascal, Cardenas, Areli, Kong, Milene, Herrera-Marschitz, Mario

2017

Overview

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.

• Publisher: Springer Nature B.V
• Subject: Amyotrophic lateral sclerosis / Astrocytes / Cell adhesion & migration / Cell migration / Connexin 43 / Glial fibrillary acidic protein / Inflammation / Kinases / Nitric-oxide synthase / Overexpression / Syndecan / Transgenic mice / Tumor necrosis factor / Tumor necrosis factor-TNF