title: Lysyl oxidase is essential for normal development and function of the respiratory system and for the integrity of elastic and collagen fibers in various tissues.
abstract: Lysyl oxidases, a family comprising LOX and four LOX-like enzymes, catalyze crosslinking of elastin and collagens. Mouse Lox was recently shown to be crucial for development of the cardiovascular system because null mice died perinatally of aortic aneurysms and cardiovascular dysfunction. We show here that Lox is also essential for development of the respiratory system and the integrity of elastic and collagen fibers in the lungs and skin. The lungs of E18.5 Lox(-/-) embryos showed impaired development of the distal and proximal airways. Elastic fibers in E18.5 Lox(-/-) lungs were markedly less intensely stained and more disperse than in the wild type, especially in the mesenchyme surrounding the distal airways, bronchioles, bronchi, and trachea, and were fragmented in pulmonary arterial walls. The organization of individual collagen fibers into tight bundles was likewise abnormal. Similar elastic and collagen fiber abnormalities were seen in the skin. Lysyl oxidase activity in cultured Lox(-/-) skin fibroblasts and aortic smooth muscle cells was reduced by approximately 80%, indicating that Lox is the main isoenzyme in these cells. LOX abnormalities may thus be critical for the pathogenesis of several common diseases, including pulmonary, skin, and cardiovascular disorders.
authors.affiliation: Collagen Research Unit, Department of Medical Biochemistry and Molecular Biology, University of Oulu, PO Box 5000, 90014 Oulu, Finland. joni.maki@oulu.fi
authors.forename: Joni M
authors.initials: JM
authors.lastname: Mäki
authors.forename: Raija
authors.initials: R
authors.lastname: Sormunen
authors.forename: Sari
authors.initials: S
authors.lastname: Lippo
authors.forename: Riitta
authors.initials: R
authors.lastname: Kaarteenaho-Wiik
authors.forename: Raija
authors.initials: R
authors.lastname: Soininen
authors.forename: Johanna
authors.initials: J
authors.lastname: Myllyharju
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000196:embryology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism* / Q000648:ultrastructure; D024042:Collagen Type I / Q000378:metabolism / Q000648:ultrastructure; D024141:Collagen Type IV / Q000378:metabolism / Q000648:ultrastructure; D017077:Culture Media, Conditioned / Q000032:analysis; D004549:Elastin / Q000378:metabolism* / Q000648:ultrastructure; D047108:Embryonic Development; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes; D006579:Heterozygote; D006720:Homozygote; D007150:Immunohistochemistry; D008168:Lung / Q000196:embryology / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000196:embryology / Q000201:enzymology / Q000378:metabolism; D008249:Protein-Lysine 6-Oxidase / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D012137:Respiratory System / Q000196:embryology / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism* / Q000648:ultrastructure; D012235:Rhodamines; D012867:Skin / Q000166:cytology / Q000196:embryology / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D024042:Collagen Type I; D024141:Collagen Type IV; D017077:Culture Media, Conditioned; D005456:Fluorescent Dyes; D012235:Rhodamines; D003094:Collagen; D004549:Elastin; D008249:Protein-Lysine 6-Oxidase