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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook 2016     Display Documents



ID: 723954.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook 2016
Collagen and elastin cross-linking is altered during aberrant late lung development associated with hyperoxia
Authors:Mizikova, I.; Ruiz-Camp, J.; Steenbock, H.; Madurga, A.; Vadasz, I.; Herold, S.; Mayer, K.; Seeger, W.; Brinckmann, J.; Morty, R. E.
Date of Publication (YYYY-MM-DD):2015-06-01
Title of Journal:Am J Physiol Lung Cell Mol Physiol
Volume:308
Issue / Number:11
Start Page:L1145
End Page:58
Audience:Not Specified
Abstract / Description:Maturation of the lung extracellular matrix (ECM) plays an important role in the formation of alveolar gas exchange units. A key step in ECM maturation is cross-linking of collagen and elastin, which imparts stability and functionality to the ECM. During aberrant late lung development in bronchopulmonary dysplasia (BPD) patients and animal models of BPD, alveolarization is blocked, and the function of ECM cross-linking enzymes is deregulated, suggesting that perturbed ECM cross-linking may impact alveolarization. In a hyperoxia (85% O2)-based mouse model of BPD, blunted alveolarization was accompanied by alterations to lung collagen and elastin levels and cross-linking. Total collagen levels were increased (by 63%). The abundance of dihydroxylysinonorleucine collagen cross-links and the dihydroxylysinonorleucine-to-hydroxylysinonorleucine ratio were increased by 11 and 18%, respectively, suggestive of a profibrotic state. In contrast, insoluble elastin levels and the abundance of the elastin cross-links desmosine and isodesmosine in insoluble elastin were decreased by 35, 30, and 21%, respectively. The lung collagen-to-elastin ratio was threefold increased. Treatment of hyperoxia-exposed newborn mice with the lysyl oxidase inhibitor beta-aminopropionitrile partially restored normal collagen levels, normalized the dihydroxylysinonorleucine-to-hydroxylysinonorleucine ratio, partially normalized desmosine and isodesmosine cross-links in insoluble elastin, and partially restored elastin foci structure in the developing septa. However, beta-aminopropionitrile administration concomitant with hyperoxia exposure did not improve alveolarization, evident from unchanged alveolar surface area and alveoli number, and worsened septal thickening (increased by 12%). These data demonstrate that collagen and elastin cross-linking are perturbed during the arrested alveolarization of developing mouse lungs exposed to hyperoxia.
Free Keywords:Aminopropionitrile/pharmacology; Animals; Bronchopulmonary Dysplasia/drug therapy/etiology/*metabolism; Collagen/*metabolism; Elastin/*metabolism; Extracellular Matrix/metabolism; Hyperoxia/complications/drug therapy/*metabolism; Lung/*growth & development/metabolism/pathology; Mice; Protein Processing, Post-Translational; Protein-Lysine 6-Oxidase/antagonists & inhibitors/metabolism; alveolarization; collagen; elastin; lung development; lysyl oxidase
External Publication Status:published
Document Type:Article
Communicated by:n.n.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Institute of Virology and Cell Biology, University of Lubeck, Lubeck, Germany; and. Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center, German Center for Lung Research, Giessen, Germany; Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center, German Center for Lung Research, Giessen, Germany; Institute of Virology and Cell Biology, University of Lubeck, Lubeck, Germany; and Department of Dermatology, University of Lubeck, Lubeck, Germany. Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center, German Center for Lung Research, Giessen, Germany; rory.morty@mpi-bn.mpg.de.
Identifiers:ISSN:1522-1504 (Electronic) 1040-0605 (Linking) %R 10.1152/ajplung.00039.2015
URL:http://www.ncbi.nlm.nih.gov/pubmed/25840994
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