Astrocytes and pericytes cooperatively maintain a capillary-like structure composed of endothelial cells on gel matrix
Astrocytes and pericytes cooperatively maintain a capillary-like structure composed of endothelial cells on gel matrix
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DOI：
10.1016/j.brainres.2011.06.039
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发表时间：
2011-08-11
期刊：
影响因子：
2.9
通讯作者：
Suzuki, Norihiro
中科院分区：
文献类型：
--
作者：
Itoh, Yoshiaki;Toriumi, Haruki;Suzuki, Norihiro
胶质血管复合体（GVC）是位于脑血流和神经网络界面的结构和功能单位。尽管其生理作用已经部分阐明，但星形胶质细胞对维持与神经元网络紧密相连的脑血管系统的贡献仍不完全清楚。为了阐明星形胶质细胞和周细胞在维持毛细血管完整性中的作用，我们开发了一种新的体外GVC模型。人脑微血管内皮细胞（EC）在凝胶基质上形成毛细血管样结构（CLS）。周细胞和星形胶质细胞一起迁移并粘附在CLS上，形成GVC样结构，周细胞位于CLS和星形胶质细胞之间。星形胶质细胞与周细胞一起抑制CLS降解的程度比单独的星形胶质细胞更大。烟曲霉素和苏拉明，血管生成抑制剂，抑制GVC的形成。PDGF受体抑制剂SU 6668抑制周细胞/星形胶质细胞迁移并加速CLS降解，而VEGF受体抑制剂SU 1498不抑制周细胞/星形胶质细胞迁移，两种类型的细胞都能长时间维持CLS。免疫组化显示，水通道蛋白4和聚集蛋白表达的连接处的EC和星形胶质细胞。这些结果表明星形胶质细胞和周细胞对于维持脑微血管系统的重要性。(C)2011 Elsevier B. V.保留所有权利。
The gliovascular complex (GVC) is a structural and functional unit located at the interface between the cerebral blood flow and neural network. Even though its physiological roles have been partially clarified, the contribution of the astroglia to maintenance of the cerebral vasculature, which is tightly wired with the neuronal network, is only incompletely understood. To elucidate the role of astrocytes and pericytes in maintaining the integrity of the capillaries, we developed a new GVC model in vitro. Human brain microvascular endothelial cells (ECs) plated on a gel matrix developed a capillary-like structure (CLS). Pericytes and astrocytes migrated together and adhered to the CLS to form a GVC-like structure with pericytes between the CLS and astrocytes. Astrocytes together with pericytes suppressed CLS degradation to a greater extent than astrocytes alone. Fumagillin and suramin, angiogenesis inhibitors, suppressed GVC formation. The PDGF receptor inhibitor SU6668 suppressed pericyte/astrocyte migration and accelerated CLS degradation, whereas the VEGF receptor inhibitor SU1498 did not suppress pericyte/astrocyte migration and both types of cells maintained the CLS for a long period of time. Immunohistochemistry revealed aquaporin-4 and agrin expression at the junction of ECs and astrocytes. These results indicate the importance of both astrocytes and pericytes for maintenance of the cerebral microvasculature. (C) 2011 Elsevier B.V. All rights reserved.