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?V?3 Integrin regulates astrocyte reactivity.


ABSTRACT:

Background

Neuroinflammation involves cytokine release, astrocyte reactivity and migration. Neuronal Thy-1 promotes DITNC1 astrocyte migration by engaging ?V?3 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 ?V?3 Integrin, Syndecan-4, P2X7R, Pannexin-1, Connexin-43, GFAP, and iNOS were observed in TNF-treated astrocytes. Silencing of ?3 Integrin prior to TNF treatment prevented Thy-1-induced migration, while ?3 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 ?V?3 Integrin and other proteins, astrocyte reactivity, and Thy-1 responsiveness. Importantly, ectopic control of ?3 Integrin levels modulates these responses regardless of inflammation.

SUBMITTER: Lagos-Cabre R 

PROVIDER: S-EPMC5622429 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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<h4>Background</h4>Neuroinflammation involves cytokine release, astrocyte reactivity and migration. Neuronal Thy-1 promotes DITNC1 astrocyte migration by engaging α<sub>V</sub>β<sub>3</sub> 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.<h4>Methods</h4>Wild-type rat astrocytes (TNF-activated) or from human SOD1<sup>G93A</sup> transgenic mice  ...[more]

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