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Open Access Research article

Measurement of matrix metalloproteinase 9-mediated Collagen type III degradation fragment as a marker of skin fibrosis

Efstathios Vassiliadis12*, Sanne Skovgård Veidal12, Natasha Barascuk12, Jhinuk Basu Mullick1, Rikke Elgaard Clausen13, Lise Larsen1, Henrik Simonsen1, Dorthe Vang Larsen1, Anne-Christine Bay-Jensen1, Toni Segovia-Silvestre1, Diana Julie Leeming1 and Morten A Karsdal1

Author Affiliations

1 Assay Development, Nordic Bioscience, Herlev Hovedgade 207, DK-2730, Copenhagen, Denmark

2 Dept. of Endocrinology, University of Southern Denmark, Kløvervænget 6, DK-5000, Odense, Denmark

3 Faculty of Science, Institute of Biology, University of Copenhagen, Tagensvej 16, DK-2200, Copenhagen Denmark

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BMC Dermatology 2011, 11:6  doi:10.1186/1471-5945-11-6

Published: 29 March 2011

Abstract

Background

The current study utilized a Bleomycin-induced model of skin fibrosis to investigate the neo-epitope CO3-610 (KNGETGPQGP), a fragment of collagen III released during matrix metalloproteinase-9 (MMP9) degradation of the protein, we have previously described as a novel biomarker for liver fibrosis. The aim was to investigate CO3-610 levels in another well characterised model of fibrosis, to better describe the biomarker in relation to additional fibrotic pathologies.

Methods

Skin fibrosis was induced by daily injections of Bleomycin to a total of 52 female C3 H mice, while control mice (n = 28) were treated with phosphate buffered saline (PBS), for 2, 4, 6 or 8 weeks. Skin fibrosis was evaluated using Visiopharm software on Sirius-red stained skin sections. Urine ELISA assays and creatinine corrections were performed to measure CO3-610 levels.

Results

CO3-610 levels were significantly higher in Bleomycin-treated vs. PBS-treated mice at each time point of termination. The mean increases were: 59.2%, P < 0.0008, at 2 weeks; 113.5%, P < 0.001, at 4 weeks; 136.8%, P < 0.0001 at 6 weeks; 157.2%, P < 0.0001 at 8 weeks). PBS-treated mice showed a non-significant increase in CO3-610 levels (mean increase for weeks 2-8 = 1.7%, P = 0.789) CO3-610 levels assayed in urine were statistically significantly correlated with Western blot analysis showing increased skin fibrosis (P < 0.0001, r = 0.65).

Conclusion

Increased levels in mouse urine of the MMP-9 mediated collagen III degradation fragment CO3-610 were correlated with skin fibrosis progression, suggesting that CO3-610 may be a potential positive biomarker to study the pathogenesis of skin fibrosis in mice.