Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Biasin, V; Wygrecka, M; Marsh, LM; Becker-Pauly, C; Brcic, L; Ghanim, B; Klepetko, W; Olschewski, A; Kwapiszewska, G.
Meprin β contributes to collagen deposition in lung fibrosis.
Sci Rep. 2017; 7(1):39969-39969
Doi: 10.1038/srep39969
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PubMed
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- Führende Autor*innen der Med Uni Graz
- Biasin Valentina
- Kwapiszewska-Marsh Grazyna
- Co-Autor*innen der Med Uni Graz
- Brcic Luka
- Marsh Leigh
- Olschewski Andrea
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- 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.
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