CASIA OpenIR  > 中国科学院分子影像重点实验室
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
Source PublicationProceedings of the National Academy of Sciences of the United States of America
2017-07-28
Volume114Issue:36Pages:E7622–E7631
Other Abstract

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.

KeywordCd146 Claudin-5 Pdgfrβ Spatiotemporal Expression Blood–brain Barrier
Indexed BySCI
Document Type期刊论文
Identifierhttp://ir.ia.ac.cn/handle/173211/19554
Collection中国科学院分子影像重点实验室
Affiliation1.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
Recommended Citation
GB/T 7714
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.
Files in This Item: Download All
File Name/Size DocType Version Access License
PNAS-2017-Chen-17108(6336KB)期刊论文作者接受稿开放获取CC BY-NC-SAView Download
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Jianan Chen]'s Articles
[Yongting Luo]'s Articles
[Hui Hui]'s Articles
Baidu academic
Similar articles in Baidu academic
[Jianan Chen]'s Articles
[Yongting Luo]'s Articles
[Hui Hui]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Jianan Chen]'s Articles
[Yongting Luo]'s Articles
[Hui Hui]'s Articles
Terms of Use
No data!
Social Bookmark/Share
File name: PNAS-2017-Chen-1710848114.pdf
Format: Adobe PDF
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.