Dysregulation of lung injury and repair in moesin-deficient mice treated with intratracheal bleomycin
Dysregulation of lung injury and repair in moesin-deficient mice treated with intratracheal bleomycin
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DOI：
10.1152/ajplung.90250.2008
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发表时间：
2008-10-01
影响因子：
4.9
通讯作者：
Hashimoto, Satoru
中科院分区：
文献类型：
--
作者：
Hashimoto, Soshi;Amaya, Fumimasa;Hashimoto, Satoru
Hashimoto S，Amaya F，松山H，Ueno H，菊池S，Tanaka M，Watanabe Y，Ebina M，Ishizaka A，Tsukita S，Hashimoto S.膜突蛋白缺陷小鼠经博莱霉素治疗后肺损伤和修复的失调。美国生理学杂志肺细胞分子生理学295：L566-L574，2008年。首次发表于2008年7月25日; doi：10.1152/ajplung.90250.2008。膜突蛋白（Moesin）属于ezrin/radixin/moesin（ERM）蛋白家族，并通过肌动蛋白细胞骨架和质膜之间的交联参与细胞功能，例如形态发生和运动。虽然膜突蛋白似乎是组织构建和修复所必需的，但其在整个身体水平上的功能仍然难以捉摸，这可能是因为ERM蛋白之间存在冗余。为了确定膜突蛋白在调节与肺损伤和修复相关的肺泡结构中所起的作用，我们检测了膜突蛋白缺陷小鼠（Msn（-/Y））和对照野生型小鼠（Msn（+/Y））的肺形态学变化以及博来霉素诱导的肺损伤和纤维化的影响。免疫组织化学分析显示，膜突蛋白是专门定位于远端肺上皮，其中埃兹蛋白和radixin在Msn（-/Y）小鼠微弱检测。与Msn（+/Y）小鼠相比，Msn（-/Y）小鼠显示肺泡结构异常，并且当用博莱霉素处理时，发生更显著的肺损伤和纤维化，以及更低的体重和存活率。此外，Msn（-/Y）小鼠具有异常的细胞因子和趋化因子基因表达，如通过实时PCR所示。这是首次报道膜突蛋白参与肺炎症和修复的调节。我们的观察结果表明，膜突蛋白关键调节肺泡结构和肺内稳态的保存。
Hashimoto S, Amaya F, Matsuyama H, Ueno H, Kikuchi S, Tanaka M, Watanabe Y, Ebina M, Ishizaka A, Tsukita S, Hashimoto S. Dysregulation of lung injury and repair in moesin-deficient mice treated with intratracheal bleomycin. Am J Physiol Lung Cell Mol Physiol 295: L566-L574, 2008. First published July 25, 2008; doi: 10.1152/ajplung.90250.2008.-Moesin belongs to the ezrin/radixin/moesin (ERM) protein family and participates in cellular functions, such as morphogenesis and motility, by cross-linking between the actin cytoskeleton and plasma membranes. Although moesin seems necessary for tissue construction and repair, its function at the whole body level remains elusive, perhaps because of redundancy among ERM proteins. To determine the role played by moesin in the modulation of pulmonary alveolar structure associated with lung injury and repair, we examined the morphological changes in the lung and the effect of bleomycin-induced lung injury and fibrosis in moesin-deficient (Msn(-/Y)) and control wild-type mice (Msn(+/Y)). Immunohistochemical analysis revealed that moesin was specifically localized in the distal lung epithelium, where ezrin and radixin were faintly detectable in Msn(-/Y) mice. Compared with Msn(+/Y) mice, Msn(-/Y) mice displayed abnormalities of alveolar architecture and, when treated with bleomycin, developed more prominent lung injury and fibrosis and lower body weight and survival rate. Furthermore, Msn(-/Y) mice had abnormal cytokine and chemokine gene expression as shown by real-time PCR. This is the first report of a functional involvement of moesin in the regulation of lung inflammation and repair. Our observations show that moesin critically regulates the preservation of alveolar structure and lung homeostasis.