Gabazza Esteban C, Kasper Michael, Ohta Kotsuke, Keane Michael, D'Alessandro-Gabazza Corina, Fujimoto Hajime, Nishii Yoichi, Nakahara Hiroki, Takagi Takehiro, Menon Anil G, Adachi Yukihiko, Suzuki Koji, Taguchi Osamu
Third Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan.
Pathol Int. 2004 Oct;54(10):774-80. doi: 10.1111/j.1440-1827.2004.01754.x.
The expression of aquaporin-5, the major water channel expressed in alveolar, tracheal, and upper bronchial epithelium, is significantly down-regulated during acute lung injury. In the present study, the expression of aquaporin-5 in two different mouse models of lung fibrosis was evaluated. Lung fibrosis was induced by intratracheal and by subcutaneous infusion of bleomycin. The expression of aquaporin-5 was investigated by immunohistochemical studies and by polymerase chain reaction. There were many cells with loss of aquaporin-5 immunoreactivity in type I alveolar epithelial cells in the mouse models of lung fibrosis. Immunohistochemistry of lung tissue in aquaporin-5 knockout mice revealed a fibrotic phenotype with increased deposition of extracellular collagen type I in thickened alveolar walls. Semiquantitative analysis of aquaporin-5 mRNA expression showed more abundant content of aquaporin-5 in the lung of the normal mouse compared to the mouse with lung fibrosis. The results of this study showed, for the first time, that chronic lung injury and lung fibrosis is associated with decreased protein and mRNA expression of aquaporin-5 in the lung.
水通道蛋白5是在肺泡、气管及上支气管上皮中表达的主要水通道,在急性肺损伤期间其表达显著下调。在本研究中,对两种不同的肺纤维化小鼠模型中水通道蛋白5的表达进行了评估。通过气管内及皮下注射博来霉素诱导肺纤维化。通过免疫组织化学研究及聚合酶链反应对水通道蛋白5的表达进行了研究。在肺纤维化小鼠模型的I型肺泡上皮细胞中有许多细胞丧失了水通道蛋白5免疫反应性。水通道蛋白5基因敲除小鼠肺组织的免疫组织化学显示出一种纤维化表型,在增厚的肺泡壁中有更多的细胞外I型胶原沉积。水通道蛋白5 mRNA表达的半定量分析显示,与肺纤维化小鼠相比,正常小鼠肺中该蛋白含量更丰富。本研究结果首次表明,慢性肺损伤及肺纤维化与肺中水通道蛋白5的蛋白质及mRNA表达降低有关。