伤肺内皮和无序纤维蛋白营业额:新近发现的途径。

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伤肺内皮和无序纤维蛋白营业额:新近发现的途径。

暴击治疗地中海。2002年5月,30日(生理):s274 - 80。

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12004248 (在PubMed

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文摘

目的:回顾通路的紊乱纤维蛋白周转,促进急性呼吸窘迫综合征的病理纤维蛋白沉积和审查的贡献内皮和肺实质细胞紊乱。此外,评估如何利用这些途径在特定的临床情况下,包括脓毒症和急性肺损伤。最后,回顾新近发现的转录后的和urokinase-dependent通路的肺纤溶系统监管。数据来源:从1966年至今医学文献发表在英语。数据概要:本地异常纤维蛋白营业额的受伤的系统性变化观察脓毒症肺概括。在这两种情况下,促凝血的反应是增加,而纤溶活性是并发抑郁。促凝血的活动增加与组织因子与因子VII / VIIa。纤溶活性的血管主要归因于组织纤溶酶原激活物,而在肺血管外的纤溶活性主要归因于尿激酶纤溶酶原激活物(uPA)。抑郁的纤溶活性在很大程度上归因于纤溶酶原激活物inhibitor-1。在脓毒症,活化蛋白C也不足,其余炎性反应,凝血障碍和抑郁的纤维蛋白溶解。 Recombinant human activated protein C (drotrecogin alfa [activated]) was successful as an intervention for sepsis in a recent phase 3 clinical trial (PROWESS). Recently, novel posttranscriptional pathways that regulate expression of uPA, its receptor (uPAR), and plasminogen activator inhibitor-1 have been identified. The responsible mechanisms involve cis-trans interactions between newly recognized messenger RNA (mRNA) binding sequences and mRNA binding proteins. A 51 nucleotide mRNA binding sequence within the coding region of uPAR mRNA interacts with a novel 50-kDa mRNA binding protein to destabilize the message. Sequences within the 3' untranslated region of uPA or plasminogen activator inhibitor-1 mRNA interact with 30- and 60-kDa proteins, respectively, to regulate message stability. All of these pathways operate in lung epithelial cells, and endothelial cells regulate uPA expression through a similar pathway. In addition, uPA itself is capable of inducing expression of other components of the fibrinolytic system, including uPAR. This observation defines another feedback loop that could amplify local fibrinolysis and other uPA- or uPAR-mediated cellular responses, including cellular proteolysis, proliferation, and directed cellular migration. CONCLUSIONS: Novel posttranscriptional pathways regulate expression of uPA, uPAR, and plasminogen activator inhibitor-1. uPA itself is capable of inducing other components of the fibrinolytic system. Some or all of these newly recognized pathways are operative in endothelial and parenchymal lung cells and may influence disordered fibrin turnover in the injured lung.

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药物靶点

药物	目标	类	生物	药理作用	行动
Drotrecogin阿尔法	纤溶酶原激活物抑制剂1	蛋白质	人类	未知的	不可用	细节