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CD146 coordinates brain endothelial cell–pericyte communication for blood–brain barrier development
Jianan Chen1,2; Yongting Luo3; Hui Hui4; Tanxi Cai1; Hongxin Huang5; Fuquan Yang1; Jing Feng1; Jingjing Zhang5; Xiyun Yan1,2
2017-07-28
发表期刊Proceedings of the National Academy of Sciences of the United States of America
卷号114期号:36页码:E7622–E7631
其他摘要

The blood–brain barrier (BBB) establishes a protective interface between the central neuronal system and peripheral blood circulation and is crucial for homeostasis of the CNS. BBB formation starts when the endothelial cells (ECs) invade the CNS and pericytes are recruited to the nascent vessels during embryogenesis. Despite the essential function of pericyte–EC interaction during BBB development, the molecular mechanisms coordinating the pericyte–EC behavior and communication remain incompletely understood. Here, we report a single cell receptor, CD146, that presents dynamic expression patterns in the cerebrovasculature at the stages of BBB induction and maturation, coordinates the interplay of ECs and pericytes, and orchestrates BBB development spatiotemporally. In mouse brain, CD146 is first expressed in the cerebrovascular ECs of immature capillaries without pericyte coverage; with increased coverage of pericytes, CD146 could only be detected in pericytes, but not in cerebrovascular ECs. Specific deletion of Cd146 in mice ECs resulted in reduced brain endothelial claudin-5 expression and BBB breakdown. By analyzing mice with specific deletion of Cd146 in pericytes, which have defects in pericyte coverage and BBB integrity, we demonstrate that CD146 functions as a coreceptor of PDGF receptor-β to mediate pericyte recruitment to cerebrovascular ECs. Moreover, we found that the attached pericytes in turn down-regulate endothelial CD146 by secreting TGF-β1 to promote further BBB maturation. These results reveal that the dynamic expression of CD146 controls the behavior of ECs and pericytes, thereby coordinating the formation of a mature and stable BBB.

关键词Cd146 Claudin-5 Pdgfrβ Spatiotemporal Expression Blood–brain Barrier
收录类别SCI
文献类型期刊论文
条目标识符http://ir.ia.ac.cn/handle/173211/19554
专题中国科学院分子影像重点实验室
作者单位1.Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences
2.College of Life Sciences, University of Chinese Academy of Sciences
3.Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University
4.Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences
5.Affiliated Hospital of Guangdong Medical University, Zhanjiang
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Jianan Chen,Yongting Luo,Hui Hui,等. CD146 coordinates brain endothelial cell–pericyte communication for blood–brain barrier development[J]. Proceedings of the National Academy of Sciences of the United States of America,2017,114(36):E7622–E7631.
APA Jianan Chen.,Yongting Luo.,Hui Hui.,Tanxi Cai.,Hongxin Huang.,...&Xiyun Yan.(2017).CD146 coordinates brain endothelial cell–pericyte communication for blood–brain barrier development.Proceedings of the National Academy of Sciences of the United States of America,114(36),E7622–E7631.
MLA Jianan Chen,et al."CD146 coordinates brain endothelial cell–pericyte communication for blood–brain barrier development".Proceedings of the National Academy of Sciences of the United States of America 114.36(2017):E7622–E7631.
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