Open AccessEndothelial genetic deletion of CD147 induces changes in the dual function of the blood‐brain barrier and is implicated in Alzheimer’s disease
Author(s) -
Wang Hao,
Lv JianJun,
Zhao Yu,
Wei HaoLin,
Zhang TianJiao,
Yang HaiJiao,
Chen ZhiNan,
Jiang JianLi
Publication year - 2021
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13659
Subject(s) - blood–brain barrier , disease , biology , neuroscience , function (biology) , transporter , dual role , neurodegeneration , pathological , cancer research , microbiology and biotechnology , medicine , central nervous system , gene , pathology , genetics , chemistry , combinatorial chemistry
Aims The blood‐brain barrier (BBB) is a specialized and indispensable structure in brain blood vessels that is damaged during Alzheimer's disease (AD). CD147 is expressed on the BBB and deeply engaged in the AD pathological process. In this study, we aimed to provide a better understanding of the roles of CD147 in BBB function in health and neurodegenerative disease. Methods and Results We measured CD147 expression in mouse brains and demonstrated that CD147 is exclusively expressed in brain endothelial cells (BECs), and its expression decreases with age. After constructing endothelial‐specific CD147 knockout mice, we performed RNA‐sequencing on BECs isolated from mice of different ages as well as a range of database analyses. We found that endothelial CD147 is essential for the dual functions of the BBB, including barrier maintenance and transporter regulation. This study also shows that CD147 plays a pivotal role in neurodegenerative diseases, particularly in AD. Conclusions Our findings suggested that targeting CD147 in BECs may represent a novel therapeutic strategy, which promoted the design of future experimental investigations and the mechanistic understanding of neurodegenerative diseases.