Journal of Neuroinflammation (Sep 2017)

αVβ3 Integrin regulates astrocyte reactivity

  • 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

DOI
https://doi.org/10.1186/s12974-017-0968-5
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 13

Abstract

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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.

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