Wang Hao, Lv Jian-Jun, Zhao Yu, Wei Hao-Lin, Zhang Tian-Jiao, Yang Hai-Jiao, Chen Zhi-Nan, Jiang Jian-Li
Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China.
CNS Neurosci Ther. 2021 May 13;27(9):1048-63. doi: 10.1111/cns.13659.
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.
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.
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.
血脑屏障（BBB）是脑血管中一种特殊且不可或缺的结构，在阿尔茨海默病（AD）期间会受到损害。CD147在血脑屏障上表达，并深度参与AD的病理过程。在本研究中，我们旨在更好地了解CD147在健康和神经退行性疾病中血脑屏障功能的作用。
我们检测了小鼠脑中CD147的表达，并证明CD147仅在脑内皮细胞（BECs）中表达，且其表达随年龄增长而降低。构建内皮特异性CD147基因敲除小鼠后，我们对从不同年龄小鼠分离的BECs进行了RNA测序以及一系列数据库分析。我们发现内皮CD147对血脑屏障的双重功能至关重要，包括屏障维持和转运体调节。本研究还表明CD147在神经退行性疾病，特别是AD中起关键作用。
我们的研究结果表明，靶向BECs中的CD147可能代表一种新的治疗策略，这促进了未来实验研究的设计以及对神经退行性疾病的机制理解。
