Gpr124 is essential for blood–brain barrier integrity in central nervous system disease
文献类型：期刊论文
| 作者 | Calvin J Kuo; Michael R Mancuso; Carolina Maie; Xibin Liang; Kanako Yuki; Lu Yang,effrey W Kwong; Junlei Chang; Jing Wang; Varsha Rao; Mario Vallon |
| 刊名 | Nature Medicine
 |
| 出版日期 | 2017 |
| 文献子类 | 期刊论文 |
| 英文摘要 | Although blood–brain barrier (BBB) compromise is central to the etiology of diverse central nervous system (CNS) disorders, endothelial receptor proteins that control BBB function are poorly defined. The endothelial G-protein-coupled receptor (GPCR) Gpr124 has been reported to be required for normal forebrain angiogenesis and BBB function in mouse embryos, but the role of this receptor in adult animals is unknown. Here Gpr124 conditional knockout (CKO) in the endothelia of adult mice did not affect homeostatic BBB integrity, but resulted in BBB disruption and microvascular hemorrhage in mouse models of both ischemic stroke and glioblastoma, accompanied by reduced cerebrovascular canonical Wnt–β-catenin signaling. Constitutive activation of Wnt–β-catenin signaling fully corrected the BBB disruption and hemorrhage defects of Gpr124-CKO mice, with rescue of the endothelial gene tight junction, pericyte coverage and extracellular-matrix deficits. We thus identify Gpr124 as an endothelial GPCR specifically required for endothelial Wnt signaling and BBB integrity under pathological conditions in adult mice. This finding implicates Gpr124 as a potential therapeutic target for human CNS disorders characterized by BBB disruption. |
| URL标识 | 查看原文 |
| 语种 | 英语 |
| 源URL | [http://ir.siat.ac.cn:8080/handle/172644/12285]  |
| 专题 | 深圳先进技术研究院_医药所 |
| 作者单位 | Nature Medicine |
| 推荐引用方式 GB/T 7714 | Calvin J Kuo,Michael R Mancuso,Carolina Maie,et al. Gpr124 is essential for blood–brain barrier integrity in central nervous system disease[J]. Nature Medicine,2017. |
| APA | Calvin J Kuo.,Michael R Mancuso.,Carolina Maie.,Xibin Liang.,Kanako Yuki.,...&Katrin Andreasson.(2017).Gpr124 is essential for blood–brain barrier integrity in central nervous system disease.Nature Medicine. |
| MLA | Calvin J Kuo,et al."Gpr124 is essential for blood–brain barrier integrity in central nervous system disease".Nature Medicine (2017). |
入库方式： OAI收割
来源：深圳先进技术研究院
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。