Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, United States of America.
PLoS One. 2019 Jul 3;14(7):e0218965. doi: 10.1371/journal.pone.0218965. eCollection 2019.
Lipocalin-2 (LCN2) is a stress protein, and can be hyper-produced by many kinds of cells after exposure to injury or disease conditions. In this study, we asked whether LCN2 may play a protective role in cerebral endothelium. After focal cerebral ischemia in rats, plasma levels of LCN2 were significantly elevated at 6, 12, and 24 hrs, and persisted until 3 days post-stroke. To assess the vascular mechanisms of LCN2, we used brain endothelial cell cultures to investigate its effects on neutrophil adhesion and endothelial barrier integrity. LCN2 did not affect neutrophil adhesion to endothelial cells either under normal conditions or after TNFα stimulation. TNFα significantly increased endothelial permeability, and LCN2 rescued endothelial permeability. Concomitantly, LCN2 restored the membrane distribution of the tight junction protein ZO-1 and the adherens junction protein VE-cadherin. Our findings suggest that elevated LCN2 in the blood after ischemic stroke might affect endothelial function, in part by reducing damage to endothelial junctional proteins and maintain blood-brain barrier integrity.
脂质运载蛋白 2（LCN2）是一种应激蛋白，在受到损伤或疾病等条件的刺激后，许多类型的细胞都会过度产生 LCN2。在这项研究中，我们想知道 LCN2 是否可能在脑内皮细胞中发挥保护作用。在大鼠局灶性脑缺血后，LCN2 的血浆水平在 6、12 和 24 小时明显升高，并持续至中风后 3 天。为了评估 LCN2 的血管机制，我们使用脑内皮细胞培养物来研究其对中性粒细胞黏附和内皮屏障完整性的影响。LCN2 在正常条件下或在 TNFα 刺激下均不影响中性粒细胞黏附在内皮细胞上。TNFα 显著增加内皮通透性，而 LCN2 可挽救内皮通透性。同时，LCN2 恢复了紧密连接蛋白 ZO-1 和黏着连接蛋白 VE-cadherin 的膜分布。我们的研究结果表明，缺血性中风后血液中 LCN2 的升高可能会影响内皮功能，部分原因是减少了对内皮连接蛋白的损伤，维持了血脑屏障的完整性。
