title: Early emphysema in the tight skin and pallid mice: roles of microfibril-associated glycoproteins, collagen, and mechanical forces.
abstract: The nature of the development of emphysema in the tight skin (Tsk) and the pallid (Pa) mice are not well understood. We assessed the mechanical and nonlinear properties of the respiratory system, the alveolar structure, and the levels of microfibril-associated glycoproteins (MAGP) 1 and 2 in Tsk mice with developmental emphysema; in Pa mice, which are thought to develop adult onset emphysema; and their background, the C57BL/6 mice, at an age of 7 wk. Minor differences between collagen-related elastic properties of the lungs of the Pa and C57BL/6 mice were seen at this early age. The lungs of the Tsk mice were significantly softer yet more nonlinear than those of the Pa and C57BL/6 mice. The MAGP-1 levels were similar in all three groups. However, the level of MAGP-2, which is associated with both fibrillin-1 and collagen, was higher in the Tsk than in the Pa mice, which also had more MAGP-2 than the C57BL/6. Both the mean and the variance of alveolar diameters were larger in the Tsk than in the other two groups, while the variance in the Pa was larger than in the C57BL/6 mice, implying early development of heterogeneity. Using a network model of the parenchyma, we linked the pathophysiologic changes in the Tsk mice to mechanical forces and failure of the alveolar walls. Our findings suggest the possibility that MAGP-2-related abnormal collagen assembly, combined with mechanical forces, is involved in the progression of emphysema in the Tsk mice.
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
authors.forename: Satoru
authors.initials: S
authors.lastname: Ito
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Bartolák-Suki
authors.forename: J Michael
authors.initials: JM
authors.lastname: Shipley
authors.forename: Harikrishnan
authors.initials: H
authors.lastname: Parameswaran
authors.forename: Arnab
authors.initials: A
authors.lastname: Majumdar
authors.forename: Bélâ
authors.initials: B
authors.lastname: Suki
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism*; D003285:Contractile Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D000071838:Fibrillin-1; D000071837:Fibrillins; D008168:Lung / Q000378:metabolism / Q000503:physiopathology*; D008170:Lung Compliance; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008840:Microfilament Proteins / Q000378:metabolism; D008954:Models, Biological; D011175:Positive-Pressure Respiration; D011650:Pulmonary Alveoli / Q000473:pathology; D011656:Pulmonary Emphysema / Q000378:metabolism / Q000503:physiopathology*; D000072260:RNA Splicing Factors; D015656:Respiratory Mechanics; D012867:Skin / Q000473:pathology; D054392:Adipokines
chemical_list: D003094:Collagen; D003285:Contractile Proteins; D016326:Extracellular Matrix Proteins; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D000072260:RNA Splicing Factors; C000605724:Fbn1 protein, mouse; D054392:Adipokines; C016598:microfibrillar protein