C-type natriuretic peptide modulates permeability of the blood–brain barrier

C型利钠肽调节血脑屏障的通透性

• 批准号: 23592100
• 负责人: NAGAYAMA Tetsuya
• 金额: $ 3.41万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592100/
• 关键词: 血液脳関門; C型ナトリウム利尿ペプチド; zonula occludens-1; JunD; ドラッグデリバリーシステム; 脳卒中; 血管内皮細胞

C-type natriuretic peptide (CNP) is abundant in brain, but its effect on blood-brain barrier (BBB) permeability has not been clarified yet. Here, we examined this effect. Transendothelial electrical resistance (TEER) of in vitro BBB model, was significantly dose dependently decreased by CNP. CNP treatment reduced both the messenger RNA and protein expressions of zonula occludens-1 (ZO-1). The effects on TEER, mRNA, and protein expressions of ZO-1 were mimicked by cyclic GMP (cGMP) analog 8-bromo-cGMP and reversed by protein kinase G (PKG) inhibitor Rp-8-CPT-cGMPS, thus implying the role of PKG and cGMP signaling in BBB function. In vivo study of mouse brain by fluorimetric analysis with intravenous administration of sodium fluorescein also showed a significant increase in BBB permeability by CNP. These findings suggest that CNP modulates the BBB permeability by altering ZO-1.

C型利钠肽（CNP）在脑内含量丰富，但其对血脑屏障（BBB）通透性的影响尚不清楚。在这里，我们研究了这种影响。CNP剂量依赖性地显著降低体外BBB模型的跨内皮电阻（TEER）。CNP处理降低了闭锁小带-1（ZO-1）的信使RNA和蛋白质表达。ZO-1对TEER、mRNA和蛋白质表达的影响被环GMP（cGMP）类似物8-溴-cGMP模拟，并被蛋白激酶G（PKG）抑制剂Rp-8-CPT-cGMPS逆转，从而暗示PKG和cGMP信号传导在BBB功能中的作用。通过荧光素钠静脉给药的荧光分析进行的小鼠脑体内研究也显示CNP显著增加了BBB通透性。这些发现表明CNP通过改变ZO-1调节BBB通透性。

项目成果

C-type natriuretic peptide modulates permeability of the blood-brain barrier

• DOI: 10.1038/jcbfm.2013.234
• 发表时间: 2014-04-01
• 期刊: JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
• 影响因子: 6.3
• 作者: Bohara, Manoj;Kambe, Yuki;Miyata, Atsuro
• 通讯作者: Miyata, Atsuro

C型ナトリウム利尿ペプチドによる血液脳関門透過性の調節

C型利钠肽对血脑屏障通透性的调节

• 发表时间: 2013
• 作者: H. Konishi;S. Mateumoto;K. Namikawa;H. Kiyama;神戸悠輝，Manoj Bohara，栗原崇，永山哲也，有田和徳，宮田篤郎
• 通讯作者: 神戸悠輝，Manoj Bohara，栗原崇，永山哲也，有田和徳，宮田篤郎