Both the Complexity of Tight Junctions and Endothelial Transcytosis Are Increased During BBB Postnatal Development in Rats.
Both the Complexity of Tight Junctions and Endothelial Transcytosis Are Increased During BBB Postnatal Development in Rats.
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大鼠出生后 BBB 发育过程中紧密连接和内皮转胞吞作用的复杂性均增加
DOI：
10.3389/fnins.2022.850857
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发表时间：
2022
影响因子：
4.3
通讯作者：
Zhang, Jiewen
中科院分区：
文献类型：
--
作者：
Li, Wei;Zou, Jinlong;Shang, Junkui;Gao, Chenhao;Sun, Ruihua;Liu, Ruijie;Cao, Huixia;Wang, Yanliang;Zhang, Jiewen
血脑屏障（BBB）由单层内皮细胞组成，为神经元的正常功能和突触传递提供了一个安全稳定的环境。BBB不是一个离散的物理屏障，而是一个复杂的、动态的、适应性强的接口。BBB在出生后的短时间内在神经环境的影响下继续成熟。然而，血脑屏障形成和维持的基本机制仍然是一个谜。早期的研究已经确定了微血管内皮的两个结构特征：特殊的紧密连接（TJ）和非常低的跨细胞囊泡转运速率。以往的研究认为BBB损伤主要是由于紧密连接的破坏，而忽略了囊泡转胞吞的作用，因此缺乏对其对血脑屏障影响的研究。因此，迫切需要更好地阐明血脑屏障内皮细胞独特的结构和功能特征，以解释血脑屏障损伤在神经系统疾病中的作用。通过分离新生、青春期和成年大鼠大脑皮层血管内皮细胞，利用RNA测序技术研究其分子特征。为了探讨血脑屏障的维持机制，我们主要从屏障形成的细胞和分子调控以及微血管内皮细胞的两个特性进行了研究。有趣的是，我们发现在血脑屏障发育过程中，虽然紧密连接逐渐成熟，但内皮细胞的转胞吞作用逐渐增强，导致血脑屏障通透性增加。本研究表明，在生理条件下，低囊泡转运在维持血脑屏障的完整性方面起着重要作用。本研究不仅总结了微血管内皮细胞的独特特性，而且阐明了血脑屏障形成和维持的机制，为中枢神经系统药物输送提供了新的治疗机会。RNA测序的原始数据保存在NCBI Sequence Read Archive数据库（PRJNA 790676）中。图形摘要提出的分子途径的图形表示。在血脑屏障发育过程中，cav-1表达逐渐上调，囊泡转胞吞作用逐渐增强。尽管紧密连接逐渐成熟，但BBB通透性仍然增加，揭示了低囊泡转胞吞在维持BBB通透性中的重要作用。
The blood-brain barrier (BBB) comprises a single layer of endothelial cells and maintains a safe and homeostatic environment for proper neuronal function and synaptic transmission. BBB is not a discrete physical barrier, but a complex, dynamic, and adaptable interface. BBB continues to mature under the influence of the neural environment within a short period of time after birth. However, the basic mechanism of BBB formation and maintenance remains a mystery. Early studies have identified two structural characteristics of microvascular endothelium: special tight junctions (TJs) and a very low transcellular vesicle transport rate. Previous studies believed that BBB damage was mainly due to the destruction of tight junctions, and the role of vesicle transcytosis was neglected, so there was a lack of research on its impact on blood-brain barrier. It is urgent to get a better clarification of the unique structural and functional characteristics of the BBB endothelium to explain the role of BBB injury in neurological diseases. RNA sequencing was used to study the molecular characterization of cerebral cortex vascular endothelium by isolating them from neonatal, adolescent and adult rats. For investigation the maintenance mechanism of the BBB, we focused on the cellular and molecular regulation of barrier formation and the two characteristics of microvascular endothelial cells. Interestingly, we found that during the development of the blood-brain barrier, although the tight junctions gradually mature, endothelial cell transcytosis is gradually enhanced, resulting in an increase in the permeability of the blood-brain barrier. This study suggested that under physiological conditions, low vesicle transport is playing an important role in maintaining the integrity of the blood-brain barrier. This study not only summarized the unique characteristics of microvascular endothelial cells, but also illustrated a clarified mechanism of the development and maintenance of BBB which can provide new therapeutic opportunities for central nervous system drug delivery. Raw data of RNA sequencing were deposited in NCBI Sequence Read Archive database (PRJNA790676). Graphical Abstract Graphical representation of the proposed molecular pathway. During BBB development, cav-1 is gradually upregulated, vesicle transcytosis is gradually increased. Although tight junctions are gradually matured, BBB permeability is still increased, revealing the important role of low vesicle transcytosis in maintaining BBB permeability.
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DOI：
10.1146/annurev-cellbio-100617-062608
发表时间：
2019-10-06
影响因子：
11.3
作者：
Langen UH;Ayloo S;Gu C
通讯作者：
Gu C
影响因子：
25
作者：
Munji, Roeben Nocon;Soung, Allison Luen;Daneman, Richard
通讯作者：
Daneman, Richard
Wnt/β-catenin信号传导控制血脑屏障的发展。
影响因子：
7.8
作者：
Liebner, Stefan;Corada, Monica;Bangsow, Thorsten;Babbage, Jane;Taddei, Andrea;Czupalla, Cathrin J.;Reis, Marco;Felici, Angelina;Wolburg, Hartwig;Fruttiger, Marcus;Taketo, Makoto M.;von Melchner, Harald;Plate, Karl Heinz;Gerhardt, Holger;Dejana, Elisabetta
通讯作者：
Dejana, Elisabetta
影响因子：
3.7
作者：
Daneman R;Zhou L;Agalliu D;Cahoy JD;Kaushal A;Barres BA
通讯作者：
Barres BA
影响因子：
7.1
作者：
Duarte Lobo, Diana;Nobre, Rui Jorge;Pereira de Almeida, Luis
通讯作者：
Pereira de Almeida, Luis