Airspace Enlargement With Airway Cell Apoptosis in Klotho Mice: A Model of Aging Lung
Airspace Enlargement With Airway Cell Apoptosis in Klotho Mice: A Model of Aging Lung
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DOI：
10.1093/gerona/63.12.1289
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发表时间：
2008-12-01
影响因子：
5.1
通讯作者：
Ouchi, Yasuyoshi
中科院分区：
文献类型：
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作者：
Ishii, Masaki;Yamaguchi, Yasuhiro;Ouchi, Yasuyoshi
纯合突变 klotho (KL-/-) 小鼠表现出多种与人类衰老相似的特征，包括肺气肿。然而，肺部与年龄相关的变化尚未完全阐明。在这里，我们研究了 2-12 周龄 KL-/- 小鼠肺的结构、功能、生化和细胞动力学变化。随着年龄的增长，KL-/-小鼠观察到均匀的空腔扩大和肺弹性回缩力降低。 2周龄时，KL-/-小鼠气道壁中的凋亡细胞大约是野生型(KL+/+)小鼠的6倍。然而，KL-/-小鼠肺的脂质过氧化和弹性蛋白酶活性并未增加。蛋白质印迹表明 KL-/- 小鼠中表皮生长因子 (EGF) 和磷酸化细胞外信号调节激酶的蛋白水平降低。这些数据表明，通过抑制 EGF 依赖性途径而显着增加气道细胞凋亡可能与 KL-/- 小鼠肺部衰老的发育有关。
Homozygous mutant klotho (KL-/-) mice exhibit various characteristics resembling those of human aging, including emphysema. However, age-related changes of lungs have not been fully elucidated. Here, we investigated the structural, functional, biochemical, and cell kinetic alterations of lungs in KL-/- mice at 2-12 weeks of age. Homogeneous airspace enlargement and decreased lung elastic recoil were observed in KL-/- mice with aging. The apoptotic cells in airway walls in KL-/- mice were approximately 6 times greater than those in wild-type (KL+/+) mice at 2 weeks of age. However, lipid peroxidation and elastase activity of lungs were not increased in KL-/- mice. Western blotting suggested that protein levels of epidermal growth factor (EGF) and phosphorylated extracellular signal-regulated kinase were decreased in KL-/- mice. These data suggest that significantly increased apoptosis of airway cells via inhibition of the EGF-dependent pathway may be involved in the development of the aging lungs in KL-/- mice.