title: Morphological mechanism of the development of pulmonary emphysema in klotho mice.
abstract: The concept of fractal geometry is useful for the analysis of irregular and complex structures often seen in nature. Here we apply this concept to investigate the structural mechanism of the development of pulmonary emphysema in the klotho mouse, which, after milk feeding, exhibits characteristics resembling aging and develops emphysema. We calculated the relationships between perimeter and size characterizing shape and between cumulative frequency and size of the terminal air spaces identified from histologic slides and found that both relations followed a power law with fractal properties. However, the fractal dimensions related to the shape and size (Dsn) in the klotho mice were significantly lower than in controls. Additionally, in the klotho mice, Dsn decreased with age without significant change in mean linear intercept. These abnormal morphological changes were restored when the klotho mice were fed with a vitamin D-deficient diet. Previously undescribed morphological model simulations showed that a random destruction, in which the destruction process occurs homogeneously in the lungs, was more consistent with the data than a correlated destruction that is usually seen in smoking-related human emphysema. These results suggest that the pathological changes in the lungs of the klotho mice are derived not from localized causes, but from systemic causes that are related to abnormal activation of vitamin D. The morphogenesis of emphysema in the klotho mice and morphological analyses using fractal geometry may contribute to the understanding of the progressive nature and cause of parenchymal destruction in human emphysema.
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kawahara 53, Shogoin, Sakyo, Kyoto, 606-8507, Japan.
authors.forename: Atsuyasu
authors.initials: A
authors.lastname: Sato
authors.forename: Toyohiro
authors.initials: T
authors.lastname: Hirai
authors.forename: Akihiro
authors.initials: A
authors.lastname: Imura
authors.forename: Naoko
authors.initials: N
authors.lastname: Kita
authors.forename: Akiko
authors.initials: A
authors.lastname: Iwano
authors.forename: Shigeo
authors.initials: S
authors.lastname: Muro
authors.forename: Yo-ichi
authors.initials: Y
authors.lastname: Nabeshima
authors.forename: Bela
authors.initials: B
authors.lastname: Suki
authors.forename: Michiaki
authors.initials: M
authors.lastname: Mishima
mesh_terms: D000375:Aging; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D017709:Fractals; D005966:Glucuronidase / Q000172:deficiency*; D000090265:Klotho Proteins; D008168:Lung / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D011656:Pulmonary Emphysema / Q000209:etiology / Q000473:pathology*; D014807:Vitamin D
chemical_list: D014807:Vitamin D; D005966:Glucuronidase; D000090265:Klotho Proteins