Pericytes contribute to the disruption of the cerebral endothelial barrier via increasing VEGF expression: implications for stroke.
Pericytes contribute to the disruption of the cerebral endothelial barrier via increasing VEGF expression: implications for stroke.
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DOI：
10.1371/journal.pone.0124362
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Yao H
中科院分区：
文献类型：
--
作者：
Bai Y;Zhu X;Chao J;Zhang Y;Qian C;Li P;Liu D;Han B;Zhao L;Zhang J;Buch S;Teng G;Hu G;Yao H
在卒中早期发生的血脑屏障(BBB)完整性的破坏不仅是卒中的后果，而且也有助于卒中的进一步发展。虽然脑微血管内皮细胞和星形胶质细胞在维持血脑屏障完整性方面发挥了重要作用，但介于内皮细胞和星形胶质细胞之间的周细胞在卒中发病机制中的研究较少。我们的结果表明，氰化钠和缺糖处理人脑微血管周细胞后，血管内皮细胞生长因子的表达增加，这是通过激活酪氨酸激酶Src，下游激活丝裂原激活的蛋白激酶和PI3K/Akt通路，进而导致NF-κB移位到细胞核中。经NaCN处理的周细胞条件培养液可使内皮细胞通透性增加，这种作用可被血管内皮生长因子中和抗体显著抑制。这些发现的体内相关性在小鼠中风模型中得到进一步证实，在该模型中，小鼠的血脑屏障完整性受到破坏，并伴随着脑组织和分离的微血管中血管内皮生长因子表达的增加。因此，这些发现提示周细胞来源的血管内皮生长因子在调节卒中时血脑屏障通透性增加中所起的作用。了解血管内皮生长因子的表达调控可以为开发潜在的中风和其他神经系统疾病的治疗靶点开辟新的途径。
Disruption of the blood-brain barrier (BBB) integrity occurring during the early onset of stroke is not only a consequence of, but also contributes to the further progression of stroke. Although it has been well documented that brain microvascular endothelial cells and astrocytes play a critical role in the maintenance of BBB integrity, pericytes, sandwiched between endothelial cells and astrocytes, remain poorly studied in the pathogenesis of stroke. Our findings demonstrated that treatment of human brain microvascular pericytes with sodium cyanide (NaCN) and glucose deprivation resulted in increased expression of vascular endothelial growth factor (VEGF) via the activation of tyrosine kinase Src, with downstream activation of mitogen activated protein kinase and PI3K/Akt pathways and subsequent translocation of NF-κB into the nucleus. Conditioned medium from NaCN-treated pericytes led to increased permeability of endothelial cells, and this effect was significantly inhibited by VEGF-neutralizing antibody. The in vivo relevance of these findings was further corroborated in the stroke model of mice wherein the mice, demonstrated disruption of the BBB integrity and concomitant increase in the expression of VEGF in the brain tissue as well as in the isolated microvessel. These findings thus suggest the role of pericyte-derived VEGF in modulating increased permeability of BBB during stroke. Understanding the regulation of VEGF expression could open new avenues for the development of potential therapeutic targets for stroke and other neurological disease.
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影响因子：
2.9
作者：
Dohgu, S;Takata, F;Kataoka, Y
通讯作者：
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影响因子：
4.8
作者：
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通讯作者：
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DOI：
10.1073/pnas.0808698106
发表时间：
2009-02-10
影响因子：
11.1
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Argaw, Azeb Tadesse;Gurfein, Blake T.;John, Gareth R.
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缺血神经元通过增加 VEGF 表达激活星形胶质细胞破坏内皮屏障
影响因子：
4.7
作者：
Li YN;Pan R;Qin XJ;Yang WL;Qi Z;Liu W;Liu KJ
通讯作者：
Liu KJ
DOI：
10.1097/00004647-199909000-00012
发表时间：
1999-09-01
影响因子：
6.3
作者：
Abumiya, T;Lucero, J;del Zoppo, GJ
通讯作者：
del Zoppo, GJ