Role of microtubules in attenuation of PepG-induced vascular endothelial dysfunction by atrial natriuretic peptide.
Role of microtubules in attenuation of PepG-induced vascular endothelial dysfunction by atrial natriuretic peptide.
复制标题
微管在心房钠尿肽减弱 PepG 诱导的血管内皮功能障碍中的作用。
DOI：
10.1016/j.bbadis.2014.10.012
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Birukova,AnnaA
中科院分区：
文献类型：
--
作者：
Tian,Yufeng;Mambetsariev,Isa;Sarich,Nicolene;Meng,Fanyong;Birukova,AnnaA
Apart from control of circulating fluid, atrial natriuretic peptide (ANP) exhibits anti-inflammatory effects in the lung. However, molecular mechanisms of ANP anti-inflammatory effects are not well-understood. Peripheral microtubule (MT) dynamics is essential for agonist-induced regulation of vascular endothelial permeability. Here we studied the role of MT-dependent signaling in ANP protective effects against endothelial cell (EC) barrier dysfunction and acute lung injury induced byStaphylococcus aureus-derived peptidoglican-G (PepG). PepG-induced vascular endothelial dysfunction was accompanied by MT destabilization and disruption of MT network. ANP attenuated PepG-induced MT disassembly, NFκB signaling and activity of MT-associated Rho activator GEF-H1 leading to attenuation of EC inflammatory activation reflected by expression of adhesion molecules ICAM1 and VCAM1. ANP-induced EC barrier preservation and MT stabilization were linked to phosphorylation and inactivation of MT-depolymerizing protein stathmin. Expression of stathmin phosphorylation-deficient mutant abolished ANP protective effects against PepG-induced inflammation and EC permeability. In contrast, siRNA-mediated stathmin knockdown prevented PepG-induced peripheral MT disassembly and endothelial barrier dysfunction. ANP protective effects in a murine model of PepG-induced lung injury were associated with increased phosphorylation of stathmin, while exacerbated lung injury in the ANP knockout mice was accompanied by decreased pool of stable MT. Stathmin knockdownin vivoreversed exacerbation of lung injury in the ANP knockout mice. These results show a novel MT-mediated mechanism of endothelial barrier protection by ANP in pulmonary EC and animal model of PepG-induced lung injury via stathmin-dependent control of MT assembly.
