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
Chen, Jianan1,2; Luo, Yongting3; Hui, Hui4; Cai, Tanxi1; Huang, Hongxin5; Yang, Fuquan1; Feng, Jing1; Zhang, Jingjing5; Yan, Xiyun1,2
Source PublicationPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2017-09-05
Volume114Issue:36Pages:E7622-E7631
SubtypeArticle
AbstractThe 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.
KeywordCd146 Claudin-5 Pdgfr Beta Spatiotemporal Expression Blood-brain Barrier
WOS HeadingsScience & Technology
DOI10.1073/pnas.1710848114
WOS KeywordGROWTH-FACTOR ; IN-VIVO ; TUMOR ANGIOGENESIS ; RECEPTOR ; CNS ; IDENTIFICATION ; HEALTH ; ESTABLISHMENT ; MICROVESSELS ; MAINTENANCE
Indexed BySCI
Language英语
Funding OrganizationNational 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)
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000409182200024
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ia.ac.cn/handle/173211/20718
Collection中国科学院分子影像重点实验室
Affiliation1.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
Recommended Citation
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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