在肺部疾病中，循环中基质金属蛋白酶-7降解的弹性蛋白水平升高。

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

作者信息

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

机构信息

Nordic Bioscience A/S, Herlev, Denmark; The Technical University of Denmark, Department of Systems Biology, Kgs. Lyngby, Denmark.

Nordic Bioscience A/S, Herlev, Denmark.

出版信息

Clin Biochem. 2015 Nov;48(16-17):1083-8. doi: 10.1016/j.clinbiochem.2015.07.009. Epub 2015 Jul 9.

DOI:10.1016/j.clinbiochem.2015.07.009

PMID:26164539

Abstract

OBJECTIVES

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.

DESIGN AND METHODS

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.

RESULTS

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<0.0001) and lung cancer (96%, p<0.0001) compared to matched controls.

CONCLUSIONS

MMP-7-generated elastin fragments can be quantified in serum and may reflect pathological lung tissue turnover in several important lung diseases.

摘要

目的

弹性蛋白是肺的标志性蛋白质。基质金属蛋白酶-7（MMP-7）在肺防御机制中起重要作用，并可降解弹性蛋白。然而，从未在肺部疾病患者中通过血清学方法对MMP-7降解弹性蛋白的活性进行定量。因此，开发了一种用于定量MMP-7产生的弹性蛋白片段（ELM7）的检测方法，以研究MMP-7介导的弹性蛋白降解在特发性肺纤维化（IPF）和肺癌等肺部疾病中的情况。

设计与方法

针对弹性蛋白上八个精心挑选的MMP-7切割位点制备单克隆抗体（mABs）。在对mABs进行表征和验证后，选择了一种靶向ELM7片段的mAB。评估了诊断为IPF（n = 123，基线样本，CTgov注册号NCT00786201）和肺癌（n = 40）患者的血清样本中的ELM7片段水平，并与年龄和性别匹配的对照组进行比较。