Meprin ? 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 meprin? and meprin? 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 meprin?, meprin? and the double meprins?? 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 meprin? KO, but not in meprin? and meprin?? KO mice. This finding was accompanied by localization of meprin? to epithelial cells in regions with immature collagen in mice. Similarly, in human IPF lungs meprin? was mostly localized in epithelium. These findings suggest that local environment triggers meprin? expression to support collagen maturation. In conclusion, our data demonstrate the in vivo relevance of meprin? in collagen deposition in lung fibrosis.

SUBMITTER: Biasin V 

PROVIDER: S-EPMC5216360 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature