Local thermal injury induces general endothelial cell contraction through p38 MAP kinase activation-猫眼课题宝

DOI：

10.1111/apm.12226

发表时间：

2014-01

期刊：

APMIS

影响因子：

2.8

通讯作者：

中科院分区：

医学3区

文献类型：

作者：

Shu-yun Wang;Qiaobing Huang;Jingxin Guo;Xiaohua Guo;Quanmei Sun;U. Brunk;Dong Han;K. Zhao;Ming Zhao

薄壁血管的内皮细胞（EC）在血液和组织之间形成屏障。作为对炎症的反应，EC连接变宽并形成间隙，导致屏障功能受损。虽然这些变化背后的机制仍然不完全清楚，但一个已知的原因是肌动球蛋白依赖性肌动蛋白重排。在这里，通过使用原子力显微镜和共聚焦显微镜方法的组合，我们是第一个报告热损伤诱导全身微静脉通透性过高，烧伤大鼠血清诱导EC肌动蛋白重排，收缩，以及紧密连接损伤。抑制p38丝裂原活化蛋白激酶（p38MAPK）可显著减少EC应力纤维形成、收缩、体积变化和紧密连接损伤，从而大大减少EC间隙的出现，从而在很大程度上改善血管功能障碍。这一发现可能对未来旨在缓解大面积烧伤后严重的全身血管功能障碍的药物治疗设计具有重要意义。

Endothelial cells (ECs) of thin‐walled blood vessels form a barrier between blood and tissue. As a response to inflammation, the EC junctions widen and gaps form, resulting in compromised barrier functions. Although the mechanisms behind the establishment of these changes are still incompletely understood, one known reason is actomyosin‐dependent actin rearrangement. Here, by using atomic force microscopy and a combination of confocal microscopy methods, we are the first to report that thermal injury induces general venular hyperpermeability and that serum from burned rats induces EC actin rearrangement, contraction, as well as tight‐junction damage. Inhibition of the p38 mitogen‐activated protein kinase (p38MAPK) largely ameliorates resulting vascular dysfunction by significantly reducing EC stress‐fiber formation, contraction, volume changes and tight‐junction damage, thereby greatly reducing the appearance of EC gaps. The findings may be of importance for the design of future pharmacotherapies aiming to ease the severe general vascular dysfunction that follows extensive burns.

Local thermal injury induces general endothelial cell contraction through p38 MAP kinase activation

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