Levels of circulating MMP-7 degraded elastin are elevated in pulmonary disorders

Elastin is a signature protein of the lungs. Matrix metalloproteinase-7 (MMP-7) is important in lung defence mechanisms and degrades elastin. However, MMP-7 activity in regard to elastin degradation has never been quantified serologically in patients with lung diseases. An assay for the quantificati...

Full description

Saved in:
Bibliographic Details
Published in:Clinical biochemistry 2015-11, Vol.48 (16-17), p.1083-1088
Main Authors: Kristensen, J.H., Larsen, L., Dasgupta, B., Brodmerkel, C., Curran, M., Karsdal, M.A., Sand, J.M.B., Willumsen, N., Knox, A.J., Bolton, C.E., Johnson, S.R., Hägglund, P., Svensson, B., Leeming, D.J.
Format: Article
Language:English
Subjects:
Aged
Animals
Case-Control Studies
Elastin
Elastin - metabolism
Female
Humans
Idiopathic pulmonary fibrosis
Idiopathic Pulmonary Fibrosis - blood
Idiopathic Pulmonary Fibrosis - metabolism
Immunology
Lung - metabolism
Lung carcinoma
Lung Diseases - blood
Lung Diseases - metabolism
Lung Neoplasms - blood
Lung Neoplasms - metabolism
Male
Matrilysin
Matrix Metalloproteinase 7 - blood
Metalloproteinases
Mice
Mice, Inbred BALB C
Middle Aged
Proteolysis
Pulmonology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Elastin is a signature protein of the lungs. Matrix metalloproteinase-7 (MMP-7) is important in lung defence mechanisms and degrades elastin. However, MMP-7 activity in regard to elastin degradation has never been quantified serologically in patients with lung diseases. An assay for the quantification of MMP-7 generated elastin fragments (ELM7) was therefore developed to investigate MMP-7 derived elastin degradation in pulmonary disorders such as idiopathic pulmonary fibrosis (IPF) and lung cancer. Monoclonal antibodies (mABs) were raised against eight carefully selected MMP-7 cleavage sites on elastin. After characterisation and validation of the mABs, one mAB targeting the ELM7 fragment was chosen. ELM7 fragment levels were assessed in serum samples from patients diagnosed with IPF (n=123, baseline samples, CTgov reg. NCT00786201), and lung cancer (n=40) and compared with age- and sex-matched controls. The ELM7 assay was specific towards in vitro MMP-7 degraded elastin and the ELM7 neoepitope but not towards other MMP-7 derived elastin fragments. Serum ELM7 levels were significantly increased in IPF (113%, p
ISSN:0009-9120
1873-2933
DOI:10.1016/j.clinbiochem.2015.07.009