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

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

30 Citas (Scopus)

Resumen

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.

Idioma originalInglés
Número de artículo194
PublicaciónJournal of Neuroinflammation
Volumen14
N.º1
DOI
EstadoPublicada - 29 sep 2017

Áreas temáticas de ASJC Scopus

  • Neurociencia (todo)
  • Inmunología
  • Neurología
  • Neurociencia celular y molecular

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