Activated endothelial cells induce a distinct type of astrocytic reactivity.
Activated endothelial cells induce a distinct type of astrocytic reactivity.
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DOI：
10.1038/s42003-022-03237-8
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发表时间：
2022-03-29
影响因子：
5.9
通讯作者：
Lasagna-Reeves CA
中科院分区：
文献类型：
--
作者：
Taylor X;Cisternas P;Jury N;Martinez P;Huang X;You Y;Redding-Ochoa J;Vidal R;Zhang J;Troncoso J;Lasagna-Reeves CA
反应性星形胶质细胞增生是星形胶质细胞对异常事件和损伤的普遍反应。研究表明，促炎性小胶质细胞可以使星形胶质细胞（称为 A1 星形胶质细胞）极化为神经毒性表型，其特征是补体成分 3 (C3) 表达增加。目前尚不清楚来自其他细胞类型的炎症刺激是否也能够诱导 C3+ 神经毒性星形胶质细胞亚群。在这里，我们发现 C3+ 神经毒性星形胶质细胞的亚型是由激活的内皮细胞诱导的，这与小胶质细胞激活的星形胶质细胞不同。此外，我们发现内皮诱导的星形胶质细胞上调了 A1 星形胶质细胞基因的表达，并表现出独特的细胞外基质重塑特征。最后，我们证明，在小鼠模型和 AD/CAA 患者中，内皮诱导的星形胶质细胞呈核心蛋白聚糖阳性，并且与血管淀粉样蛋白沉积相关，但与实质淀粉样斑块无关。这些发现表明 C3+ 反应性星形胶质细胞存在潜在广泛且微妙的功能多样性。受损的内皮细胞会在星形胶质细胞中诱导 A1 表型，其特征是与细胞外基质重塑因子（例如核心蛋白聚糖和血管 Aß 沉积物）相关的遗传特征。
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. Injured endothelial cells are shown to induce an A1 phenotype in astrocytes, characterized by a genetic signature associated with extracellular matrix remodeling factors (e.g. decorin and vascular Aß deposits).
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影响因子：
14.8
作者：
Beaudoin, Gerard M. J., III;Lee, Seung-Hye;Arikkath, Jyothi
通讯作者：
Arikkath, Jyothi
影响因子：
25
作者：
Hasel, Philip;Rose, Indigo V. L.;Liddelow, Shane A.
通讯作者：
Liddelow, Shane A.
脑淀粉样血管病对内皮的影响。
影响因子：
3.9
作者：
Grinberg, Lea Tenenholz;Korczyn, Amos D.;Heinsen, Helmut
通讯作者：
Heinsen, Helmut
影响因子：
5.6
作者：
Cabral-Pacheco GA;Garza-Veloz I;Castruita-De la Rosa C;Ramirez-Acuña JM;Perez-Romero BA;Guerrero-Rodriguez JF;Martinez-Avila N;Martinez-Fierro ML
通讯作者：
Martinez-Fierro ML
影响因子：
6.1
作者：
Garcia-Alloza, Monica;Robbins, Elissa M.;Frosch, Matthew P.
通讯作者：
Frosch, Matthew P.