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

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. Th...

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Published in:BMC dermatology 2011-03, Vol.11 (1), p.6-6, Article 6
Main Authors: Vassiliadis, Efstathios, Veidal, Sanne Skovgård, Barascuk, Natasha, Mullick, Jhinuk Basu, Clausen, Rikke Elgaard, Larsen, Lise, Simonsen, Henrik, Larsen, Dorthe Vang, Bay-Jensen, Anne-Christine, Segovia-Silvestre, Toni, Leeming, Diana Julie, Karsdal, Morten A
Format: Article
Language:English
Subjects:
Animals
Biomarkers
Biomarkers - urine
Bleomycin
Collagen
Collagen Type III - urine
Diagnosis
Enzyme-Linked Immunosorbent Assay - methods
Epitopes - urine
Ethanol
Extracellular Matrix
Female
Fibrosis
Fibrosis - chemically induced
Fibrosis - metabolism
Fibrosis - pathology
Histology
Immunoassay
Matrix Metalloproteinase 9 - physiology
Mice
Mice, Inbred C3H
Pathogenesis
Physiological aspects
Proteases
Proteolysis
Skin Diseases - chemically induced
Skin Diseases - metabolism
Skin Diseases - pathology
Statistical analysis
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Summary: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. 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. 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). 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.
ISSN:1471-5945
1471-5945
DOI:10.1186/1471-5945-11-6