来源：生物谷 2012-05-25 19:28
急性炎症性疾病如败血症以及诸如糖尿病、关节炎等慢性炎症性疾病都是由一个持续的血管壁炎症而导致的。近日，布里格姆妇女医院（BWH）的研究人员发现一种microRNA（小非编码RNA分子）——miR-181b可以减少此类疾病的炎症反应。
Mark Feinberg为首的研究团队表示：研究结果将有助于抗炎疗法的发展。
这项研究发表在5月24日的Journal of Clinical Investigation杂志上。
研究人员发现在患败血症小鼠和危重病人中miR-181b的表达降低了。
microRNA-181b每增加一个单位，败血症的可能性就会减少，这表明较高水平的miR-181b可能防治败血症。
NF-kB是调节炎症反应的一个重要信号通路因子。研究人员发现在血管壁上，miR-181b是这条信号途径的有力调节因子。 miR-181b作用于importin-alpha3，后者对NF-kB信号至关重要。
miR-181b的过表达会抑制importin alpha3以及参与NF-kB信号通路的其他分子的表达，从而减少炎症反应。
研究人员发现给败血症小鼠后静脉注射miR-181b。结果发现小鼠生存率升高，同时能降低脓毒症小鼠肺部炎症损伤。
研究人员表示：我们相信microRNAs如 miR-181b可能是治疗血管炎症性疾病的有效靶标。（生物谷：Bioon.com）
MicroRNA-181b regulates NF-κB–mediated vascular inflammation
Xinghui Sun, Basak Icli, Akm Khyrul Wara, Nathan Belkin, Shaolin He, Lester Kobzik, Gary M. Hunninghake, Miguel Pinilla Vera, MICU Registry, Timothy S. Blackwell, Rebecca M. Baron and Mark W. Feinberg
EC activation and dysfunction have been linked to a variety of vascular inflammatory disease states. The function of microRNAs (miRNAs) in vascular EC activation and inflammation remains poorly understood. Herein, we report that microRNA-181b (miR-181b) serves as a potent regulator of downstream NF-κB signaling in the vascular endothelium by targeting importin-α3, a protein that is required for nuclear translocation of NF-κB. Overexpression of miR-181b inhibited importin-α3 expression and an enriched set of NF-κB–responsive genes such as adhesion molecules VCAM-1 and E-selectin in ECs in vitro and in vivo. In addition, treatment of mice with proinflammatory stimuli reduced miR-181b expression. Rescue of miR-181b levels by systemic administration of miR-181b “mimics” reduced downstream NF-κB signaling and leukocyte influx in the vascular endothelium and decreased lung injury and mortality in endotoxemic mice. In contrast, miR-181b inhibition exacerbated endotoxin-induced NF-κB activity, leukocyte influx, and lung injury. Finally, we observed that critically ill patients with sepsis had reduced levels of miR-181b compared with control intensive care unit (ICU) subjects. Collectively, these findings demonstrate that miR-181b regulates NF-κB–mediated EC activation and vascular inflammation in response to proinflammatory stimuli and that rescue of miR-181b expression could provide a new target for antiinflammatory therapy and critical illness.
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