title: Meprin β contributes to collagen deposition in lung fibrosis.
abstract: Lung fibrosis is a severe disease characterized by epithelial cell injury, inflammation and collagen deposition. The metalloproteases meprinα and meprinβ have been shown to enhance collagen maturation and inflammatory cell infiltration via cleavage of cell-cell contact molecules; therefore we hypothesized that meprins could play a role in lung fibrosis. An exhaustive characterization of bleomycin-treated meprinα, meprinβ and the double meprinsαβ knock-out (KO) with respective wt-littermates was performed by using several different methods. We observed no difference in lung function parameters and no change in inflammatory cells infiltrating the lung between wt and all meprins KO mice after 14 days bleomycin. No difference in epithelial integrity as assessed by e-cadherin protein level was detected in bleomycin-treated lungs. However, morphological analysis in the bleomycin-treated mice revealed decrease collagen deposition and tissue density in meprinβ KO, but not in meprinα and meprinαβ KO mice. This finding was accompanied by localization of meprinβ to epithelial cells in regions with immature collagen in mice. Similarly, in human IPF lungs meprinβ was mostly localized in epithelium. These findings suggest that local environment triggers meprinβ expression to support collagen maturation. In conclusion, our data demonstrate the in vivo relevance of meprinβ in collagen deposition in lung fibrosis.
authors.affiliation: Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
authors.forename: V
authors.initials: V
authors.lastname: Biasin
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Giessen Lung Center, Giessen, Germany.|German Centre for Lung Research (DZL), Giessen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Wygrecka
authors.affiliation: Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
authors.forename: L M
authors.initials: LM
authors.lastname: Marsh
authors.affiliation: Institute of Biochemistry, Unit for Degradomics of the Protease Web, University of Kiel, Kiel, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Becker-Pauly
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz Austria.
authors.forename: L
authors.initials: L
authors.lastname: Brcic
authors.affiliation: Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.|Department of Surgery, Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Ghanim
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz Austria.
authors.forename: W
authors.initials: W
authors.lastname: Klepetko
authors.affiliation: Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.|Department of Physiology, Medical University of Graz, Graz, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Olschewski
authors.affiliation: Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.|Department of Physiology, Medical University of Graz, Graz, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Kwapiszewska
mesh_terms: D000072283:A549 Cells; D000818:Animals; D001761:Bleomycin / Q000009:adverse effects; D003094:Collagen / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D008666:Metalloendopeptidases / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D003094:Collagen; D008666:Metalloendopeptidases; C053833:meprin A