Transforming growth factor-β:: A mediator of cell regulation in acute respiratory distress syndrome
Transforming growth factor-β:: A mediator of cell regulation in acute respiratory distress syndrome
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DOI：
10.1097/01.ccm.0000057901.92381.75
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发表时间：
2003-04-01
影响因子：
8.8
通讯作者：
Chiche, JD
中科院分区：
文献类型：
--
作者：
Dhainaut, JF;Charpentier, J;Chiche, JD
目的：回顾转化生长因子（TGF）-β在急性肺损伤中的应用的最新进展，并应用这些知识来理解这种综合征的病理生理学。数据来源和研究选择：发表的研究和评论文章，英语语言相关的TGF-β在急性肺损伤中的作用。数据提取和合成：细胞因子TGF-β在包括肺在内的多个器官的组织损伤的解决中起着关键作用。损伤后，TGF-β在组织修复的晚期阶段得到了最彻底的评估，在那里它在肺纤维化的发展中起着关键作用。相比之下，最近的动物研究表明，几个TGF-β诱导基因的表达水平显着增加，早在诱导损伤后2天。整合素α（v）β（6）激活肺中潜伏的TGF-β。在博来霉素诱导的急性肺损伤模型中，缺乏这种整合素的小鼠完全免于肺水肿。TGF-β的药理学抑制也保护野生型小鼠免受博莱霉素或大肠杆菌内毒素诱导的肺水肿。在一项评估急性呼吸窘迫综合征（ARDS）过程中支气管肺泡灌洗液中TGF-β的临床研究中，也报告了类似的发现。事实上，支气管肺泡灌洗液浓度在ARDS标准开始后1天就显著增加，并与Pa 0（2）/FI 0（2）比值的降低相关，表明TGF-β 1在人类ARDS的发展中起重要作用。这些研究表明，TGF-β不仅参与了急性肺损伤的晚期，而且可能在急性肺损伤的早期是活跃的，并可能导致肺水肿的发展。整合素介导的TGF-β的局部活化对ARDS中肺水肿的发展至关重要，阻断TGF-β或其活化可能是治疗这种疾病的有效方法。
Objective: To review recent advances in the use of transforming growth factor (TGF)-beta in acute lung injury and to apply this knowledge to understanding the pathophysiology of this syndrome.Data Sources and Study Selection: Published research and review articles in, the English language related to the role of TGF-beta in acute lung injury.Data Extraction and Synthesis: The cytokine TGF-beta plays a critical role in the resolution of tissue injury in multiple organs, including the lung. Following injury, TGF-beta has been most thoroughly evaluated during the late phases of tissue repair, where it plays a critical role in the development of pulmonary fibrosis. In contrast, recent animal studies showed that expression levels of several TGF-beta-inducible genes were dramatically increased as early as 2 days after the induction of injury. The integrin alpha(v)beta(6) activates latent TGF-beta in the lungs. Mice lacking this integrin were completely protected from pulmonary edema in a model of bleomycin-induced acute lung injury. Pharmacologic inhibition of TGF-beta also protected wild-type mice from pulmonary edema induced by bleomycin or Escherichia coli endotoxin. Similar findings also have been reported in patients in a clinical study evaluating TGF-beta in the bronchoalveolar lavage fluid during the course of acute respiratory distress syndrome (ARDS). Indeed, the bronchoalveolar lavage concentrations were dramatically increased as early as 1 day after the initiation of ARDS criteria and were correlated with decreases in the Pa0(2)/FI0(2) ratio, suggesting an important role for TGF-b1 in the development of ARDS in humans.Conclusions: These studies suggest that TGF-beta not only participates in the late phase of acute lung injury, but also might be active early in acute lung injury and potentially could contribute to the development of pulmonary edema. Integrin-mediated local activation of TGF-beta is critical to the development of pulmonary edema in ARDS, and blocking TGF-beta or its activation could be an effective treatment for this disorder.