Expression of periaxin (PRX) specifically in the human cerebrovascular system: PDZ domain-mediated strengthening of endothelial barrier function.
Expression of periaxin (PRX) specifically in the human cerebrovascular system: PDZ domain-mediated strengthening of endothelial barrier function.
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DOI：
10.1038/s41598-018-28190-7
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发表时间：
2018-07-03
影响因子：
4.6
通讯作者：
Andjelkovic AV
中科院分区：
文献类型：
--
作者：
Wang MM;Zhang X;Lee SJ;Maripudi S;Keep RF;Johnson AM;Stamatovic SM;Andjelkovic AV
脑内皮细胞功能的调节在血脑屏障通透性的变化中起着至关重要的作用。对于建立内皮紧密连接重要的蛋白质已经成为关键分子，并且含有PDZ结构域的分子是其中最重要的。我们已经发现，PDZ结构域含有蛋白质周蛋白（PRX）表达在人脑内皮细胞。令人惊讶的是，PRX蛋白在其他哺乳动物物种的脑内皮中未检测到，这表明它可以赋予人类特异性血管特性。在内皮细胞中，PRX主要定位于细胞核而不是紧密连接。转录组分析表明，PRX表达抑制，至少50%，一组炎症标志物，其中70%是I型干扰素反应基因，只有四个基因显着激活PRX表达。当在小鼠内皮细胞中表达时，PRX增强屏障功能，显著增加跨内皮电阻（~35%; p < 0.05），并降低多种分子的渗透性。PRX的PDZ结构域对于其屏障增强性质是必要的和足够的，因为仅含有PDZ结构域的剪接变体（S-PRX）也增加屏障功能。PRX还减弱脂多糖的渗透性增强作用。总的来说，这些研究表明，PRX可能通过调节炎症基因程序来调节人脑内皮细胞的内皮稳态。
Regulation of cerebral endothelial cell function plays an essential role in changes in blood-brain barrier permeability. Proteins that are important for establishment of endothelial tight junctions have emerged as critical molecules, and PDZ domain containing-molecules are among the most important. We have discovered that the PDZ-domain containing protein periaxin (PRX) is expressed in human cerebral endothelial cells. Surprisingly, PRX protein is not detected in brain endothelium in other mammalian species, suggesting that it could confer human-specific vascular properties. In endothelial cells, PRX is predominantly localized to the nucleus and not tight junctions. Transcriptome analysis shows that PRX expression suppresses, by at least 50%, a panel of inflammatory markers, of which 70% are Type I interferon response genes; only four genes were significantly activated by PRX expression. When expressed in mouse endothelial cells, PRX strengthens barrier function, significantly increases transendothelial electrical resistance (~35%; p < 0.05), and reduces the permeability of a wide range of molecules. The PDZ domain of PRX is necessary and sufficient for its barrier enhancing properties, since a splice variant (S-PRX) that contains only the PDZ domain, also increases barrier function. PRX also attenuates the permeability enhancing effects of lipopolysaccharide. Collectively, these studies suggest that PRX could potentially regulate endothelial homeostasis in human cerebral endothelial cells by modulating inflammatory gene programs.
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三个紧密连接相关的Maguks ZO-1，ZO-2和ZO-3与Claudins的Cooh Termini直接结合。
DOI：
10.1083/jcb.147.6.1351
发表时间：
1999-12-13
期刊：
The Journal of cell biology
影响因子：
--
作者：
Itoh M;Furuse M;Morita K;Kubota K;Saitou M;Tsukita S
通讯作者：
Tsukita S
影响因子：
16.2
作者：
GILLESPIE, CS;SHERMAN, DL;BROPHY, PJ
通讯作者：
BROPHY, PJ
影响因子：
3.2
作者：
Alanne, Maria H.;Pummi, Kati;Peltonen, Sirkku
通讯作者：
Peltonen, Sirkku
影响因子：
4.8
作者：
Dytrych, L;Sherman, DL;Brophy, PJ
通讯作者：
Brophy, PJ
影响因子：
3.5
作者：
Guilbot, A;Williams, A;Claustres, M
通讯作者：
Claustres, M