αVβ3 Integrin regulates astrocyte reactivity
2017; BioMed Central; Volume: 14; Issue: 1 Linguagem: Inglês
10.1186/s12974-017-0968-5
ISSN1742-2094
AutoresRaúl Lagos‐Cabré, Álvaro Álvarez, Milene Kong, Francesca Burgos‐Bravo, Areli Cárdenas, Edgardo Rojas-Mancilla, Ramón Pérez-Núñez, Rodrigo Herrera‐Molina, Fabiola Rojas, Pascal Schneider, Mario Herrera‐Marschitz, Andrew F. G. Quest, Brigitte van Zundert, Lisette Leyton,
Tópico(s)Neuroinflammation and Neurodegeneration Mechanisms
ResumoNeuroinflammation 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. 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. 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. 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.
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