αVβ3 Integrin regulates astrocyte reactivity

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).