TGF-β is a critical mediator of acute lung injury
TGF-β is a critical mediator of acute lung injury
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DOI：
10.1172/jci11963
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发表时间：
2001-06-01
影响因子：
15.9
通讯作者：
Sheppard, D
中科院分区：
文献类型：
--
作者：
Pittet, JF;Griffiths, MJD;Sheppard, D
我们已经表明，整合素α v β G激活肺和皮肤中的潜伏TGF-β。我们在这里表明，缺乏这种整合素的小鼠在博莱霉素诱导的急性肺损伤（ALI）模型中完全免受肺水肿的影响。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。TGF-β通过细胞内谷胱甘肽耗竭的机制直接增加体外肺泡上皮细胞的通透性。这些数据表明，整合素介导的TGF-β的局部活化对ALI中肺水肿的发展至关重要，并且阻断TGF-β或其活化可能是这种目前无法治疗的疾病的有效治疗方法。
We have shown that the integrin alphav betaG activates latent TGF-beta in the lungs and skin. We show here that mice lacking this integrin are completely protected from pulmonary edema in a model of bleomycin-induced acute lung injury (ALI). Pharmacologic inhibition of TGF-beta also protected wild-type mice from pulmonary edema induced by bleomycin or Escherichia coli endotoxin. TGF-beta directly increased alveolar epithelial permeability in vitro by a mechanism that involved depletion of intracellular glutathione. These data suggest that integrin-mediated local activation of TGF-beta is critical to the development of pulmonary edema in ALI and that blocking TGF-beta or its activation could be effective treatments for this currently untreatable disorder.