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Updated: Mar 9, 2026
Refined Murine Model of Idiopathic Pulmonary Fibrosis
Published on: June 17, 2025
Meprin β contributes to collagen deposition in lung fibrosis
V Biasin1, M Wygrecka2,3, L M Marsh1
1Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
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.
Insights
Meprin-beta, not meprin-alpha, contributes to lung fibrosis by promoting collagen deposition. This study highlights meprin-beta
Area of Science:
- Biochemistry
- Cell Biology
- Pulmonary Medicine
Background:
- Lung fibrosis involves epithelial injury, inflammation, and collagen deposition.
- Metalloproteases meprin-alpha and meprin-beta may influence fibrosis by cleaving cell-cell contacts.
- Meprins' role in lung fibrosis remains largely unexplored.
Purpose of the Study:
- To investigate the role of meprin-alpha and meprin-beta in the development of lung fibrosis.
- To determine if meprin knockout mice exhibit altered responses to bleomycin-induced lung injury.
Main Methods:
- Bleomycin-induced lung fibrosis model in wild-type (wt) and meprin-alpha, meprin-beta, and meprin-alpha/beta knockout (KO) mice.
- Assessment of lung function, inflammatory cell infiltration, epithelial integrity (e-cadherin), and collagen deposition.
- Immunohistochemical analysis of meprin-beta localization in mouse and human fibrotic lung tissue.
Main Results:
- No significant differences in lung function or inflammatory cell infiltration were observed between wt and meprin KO mice.
- Epithelial integrity remained unchanged across all groups after bleomycin treatment.
- Meprin-beta knockout mice showed reduced collagen deposition and tissue density compared to wt mice.
- Meprin-beta was localized to epithelial cells near immature collagen in mouse lungs and in human idiopathic pulmonary fibrosis (IPF) lungs.
Conclusions:
- Meprin-beta plays a significant role in collagen deposition during lung fibrosis.
- Meprin-beta's localization suggests it supports collagen maturation in response to local environmental cues.
- Targeting meprin-beta may offer a therapeutic strategy for lung fibrosis.
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