急性肺损伤期间的钙通量和内皮功能障碍：治疗的一个有潜力的靶点。
Calcium flux and endothelial dysfunction during acute lung injury: a STIMulating target for therapy.
机构信息
Cardiovascular Research Institute and Department of Medicine, UCSF, San Francisco, California 94143, USA.
出版信息
J Clin Invest. 2013 Mar;123(3):1015-8. doi: 10.1172/JCI68093. Epub 2013 Feb 22.
Abstract
Bacterial pathogen-associated molecular pattern molecules (PAMPs) such as LPS activate the endothelium and can lead to lung injury, but the signaling pathways mediating endothelial injury remain incompletely understood. In a recent issue of the JCI, Gandhirajan et al. identify STIM1, an ER calcium sensor, as a key link between LPS-induced ROS, calcium oscillations, and endothelial cell (EC) dysfunction. In addition, they report that BTP2, an inhibitor of calcium channels, attenuates lung injury. This study identifies a novel endothelial signaling pathway that could be a future target for the treatment of lung injury.
摘要
细菌病原体相关分子模式分子（PAMPs），如 LPS，可激活内皮细胞，导致肺损伤，但介导内皮细胞损伤的信号通路仍不完全清楚。在最近的 JCI 中，Gandhirajan 等人确定了 STIM1，一种内质网钙传感器，作为 LPS 诱导的 ROS、钙振荡和内皮细胞（EC）功能障碍之间的关键联系。此外，他们还报告了钙通道抑制剂 BTP2 可减轻肺损伤。这项研究确定了一种新的内皮信号通路，它可能成为治疗肺损伤的未来靶点。
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2
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Crit Care. 2012 Oct 4;16(5):R182. doi: 10.1186/cc11666.
3
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4
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Nat Rev Mol Cell Biol. 2012 Sep;13(9):549-65. doi: 10.1038/nrm3414.
5
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6
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7
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8
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