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CD146 coordinates brain endothelial cell-pericyte communication for blood-brain barrier development

文献类型：期刊论文

作者Chen, Jianan1,2; Luo, Yongting3; Hui, Hui4; Cai, Tanxi1; Huang, Hongxin5; Yang, Fuquan1; Feng, Jing1; Zhang, Jingjing5; Yan, Xiyun1,2
刊名PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
出版日期2017-09-05
卷号114期号:36页码:E7622-E7631
关键词Cd146 Claudin-5 Pdgfr Beta Spatiotemporal Expression Blood-brain Barrier
DOI10.1073/pnas.1710848114
文献子类Article
英文摘要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-beta to mediate pericyte recruitment to cerebrovascular ECs. Moreover, we found that the attached pericytes in turn down-regulate endothelial CD146 by secreting TGF-beta 1 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.
WOS关键词GROWTH-FACTOR ; IN-VIVO ; TUMOR ANGIOGENESIS ; RECEPTOR ; CNS ; IDENTIFICATION ; HEALTH ; ESTABLISHMENT ; MICROVESSELS ; MAINTENANCE
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000409182200024
资助机构National Basic Research Program of China 973 Programs(2015CB553705 ; National Natural Science Foundation of China(31370824 ; Chinese Academy of Sciences(XDA12020207 ; Guangdong Natural Science Fund for Distinguished Young Scholars, China ; Novo Nordisk-Chinese Academy of Sciences(NNCAS-2015-11) ; 2014CBA02003) ; 81371025 ; XDA12030202) ; 91529306 ; 81371330 ; 91640112 ; 31670185 ; 81527805 ; 81671851 ; 81502547)
源URL[http://ir.ia.ac.cn/handle/173211/20718]  
专题自动化研究所_中国科学院分子影像重点实验室
作者单位1.Chinese Acad Sci, Inst Biophys, Key Lab Prot & Peptide Pharmaceut, Beijing 100101, Peoples R China
2.Univ Chinese Acad Sci, Coll Life Sci, Beijing 100049, Peoples R China
3.China Agr Univ, Beijing Adv Innovat Ctr Food Nutr & Human Hlth, Beijing 100193, Peoples R China
4.Chinese Acad Sci, Inst Automat, Key Lab Mol Imaging, Beijing 100190, Peoples R China
5.Guangdong Med Univ, Affiliated Hosp, Zhanjiang 524001, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Jianan,Luo, Yongting,Hui, Hui,et al. 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 Chen, Jianan.,Luo, Yongting.,Hui, Hui.,Cai, Tanxi.,Huang, Hongxin.,...&Yan, Xiyun.(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 Chen, Jianan,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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来源：自动化研究所

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