Airspace enlargement with airway cell apoptosis in klotho mice: a model of aging lung.
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.
Ishii
Masaki
M
Department of Geriatric Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
Yamaguchi
Yasuhiro
Y
Yamamoto
Hiroshi
H
Hanaoka
Yoko
Y
Ouchi
Yasuyoshi
Y
D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid; D004815:Epidermal Growth Factor / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D008170:Lung Compliance / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D023421:Models, Animal; D010196:Pancreatic Elastase / Q000378:metabolism
D004815:Epidermal Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D010196:Pancreatic Elastase