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Holm, A.T.* ; Wulf-Johansson, H.* ; Hvidtsen, S.* ; Jorgensen, P.T.* ; Schlosser, A.* ; Pilecki, B.* ; Ormhoj, M.* ; Moeller, J.B.* ; Johannsen, C.* ; Baun, C.* ; Andersen, T.* ; Schneider, J.P.* ; Hegermann, J.* ; Ochs, M.* ; Götz, A.A.* ; Schulz, H. ; Hrabě de Angelis, M. ; Vestbo, J.* ; Holmskov, U.* ; Sorensen, G.L.*

Characterization of spontaneous air space enlargement in mice lacking microfibrillar-associated protein 4.

Am. J. Physiol. Lung Cell Mol. Physiol. 308, L1114-L1124 (2015)
Postprint DOI PMC
Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
Microfibrillar-associated protein 4 (MFAP4) is localized to elastic fibers in blood vessels and the interalveolar septa of the lungs and is further present in bronchoalveolar lavage. Mfap4 has been previously suggested to be involved in elastogenesis in the lung. We tested this prediction and aimed to characterize the pulmonary function changes and emphysematous changes that occur in Mfap4 deficient (Mfap4-/-) mice. Significant changes included increases in total lung capacity and compliance, which were evident in Mfap4-/- mice at 6 months and 8 months, but not at 3 months of age. Using in vivo breath-hold gated micro-computed tomography (micro-CT) in 8-month-old Mfap4-/- mice, we found that the mean density of the lung parenchyma was decreased, and the low-attenuation area (LAA) was significantly increased by 14 % compared to Mfap4+/+ mice. Transmission electron microscopy (TEM) did not reveal differences in the organization of elastic fibers, and there was no difference in elastin content, but borderline significant increase in elastin mRNA expression in 3-month-old mice. Stereological analysis showed that alveolar surface density in relation to the lung parenchyma and total alveolar surface area inside of the lung were both significantly decreased in Mfap4-/- mice by 25 % and 15 %, respectively. The data did not support an essential role of MFAP4 in pulmonary elastic fiber organization or content, but indicated increased turnover in young Mfap4-/- mice. However, Mfap4-/- mice developed a spontaneous loss of lung function, which was evident at 6 months of age, and moderate airspace enlargement, with emphysema-like changes.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Mfap4 ; Air Space Enlargement ; Gene Deficiency; Obstructive Pulmonary-disease; Elastase-induced Emphysema; Computed-tomography; Glycoprotein Magp-36; Lung Morphology; Binding Protein; Gene-expression; Murine Model; Localization; Progression
Language
Publication Year 2015
HGF-reported in Year 2015
ISSN (print) / ISBN 1040-0605
e-ISSN 1522-1504
Journal American Journal of Physiology - Lung Cellular and Molecular Physiology
Quellenangaben Volume: 308, Issue: 11, Pages: L1114-L1124 Article Number: , Supplement: ,
Publisher American Physiological Society
Publishing Place Bethesda, Md. [u.a.]
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)
Institute of Epidemiology (EPI)
POF-Topic(s) 30201 - Metabolic Health
30503 - Chronic Diseases of the Lung and Allergies
Research field(s) Genetics and Epidemiology
PSP Element(s) G-500600-001
G-503900-003
DOI 10.1152/ajplung.00351.2014
WOS ID WOS:000357509200003
Scopus ID 84930837223
PubMed ID 26033354
Erfassungsdatum 2015-04-20
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