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Activated endothelial cells induce a distinct type of astrocytic reactivity.

ABSTRACT: Reactive astrogliosis is a universal response of astrocytes to abnormal events and injuries. Studies have shown that proinflammatory microglia can polarize astrocytes (designated A1 astrocytes) toward a neurotoxic phenotype characterized by increased Complement Component 3 (C3) expression. It is still unclear if inflammatory stimuli from other cell types may also be capable of inducing a subset of C3⁺ neurotoxic astrocytes. Here, we show that a subtype of C3⁺ neurotoxic astrocytes is induced by activated endothelial cells that is distinct from astrocytes activated by microglia. Furthermore, we show that endothelial-induced astrocytes have upregulated expression of A1 astrocytic genes and exhibit a distinctive extracellular matrix remodeling profile. Finally, we demonstrate that endothelial-induced astrocytes are Decorin-positive and are associated with vascular amyloid deposits but not parenchymal amyloid plaques in mouse models and AD/CAA patients. These findings demonstrate the existence of potentially extensive and subtle functional diversity of C3⁺-reactive astrocytes.

SUBMITTER: Taylor X

PROVIDER: S-EPMC8964703 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Activated endothelial cells induce a distinct type of astrocytic reactivity.

Taylor Xavier X Cisternas Pablo P Jury Nur N Martinez Pablo P Huang Xiaoqing X You Yanwen Y Redding-Ochoa Javier J Vidal Ruben R Zhang Jie J Troncoso Juan J Lasagna-Reeves Cristian A CA

Communications biology 20220329 1

Reactive astrogliosis is a universal response of astrocytes to abnormal events and injuries. Studies have shown that proinflammatory microglia can polarize astrocytes (designated A1 astrocytes) toward a neurotoxic phenotype characterized by increased Complement Component 3 (C3) expression. It is still unclear if inflammatory stimuli from other cell types may also be capable of inducing a subset of C3<sup>+</sup> neurotoxic astrocytes. Here, we show that a subtype of C3<sup>+</sup> neurotoxic ast ...[more]

PMID: 35351973

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Activated endothelial cells induce a distinct type of astrocytic reactivity.

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Activated endothelial cells induce a distinct type of astrocytic reactivity.

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