Levels of circulating MMP-7 degraded elastin are elevated in pulmonary disorders
Levels of circulating MMP-7 degraded elastin are elevated in pulmonary disorders
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DOI：
10.1016/j.clinbiochem.2015.07.009
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发表时间：
2015-11-01
影响因子：
2.8
通讯作者：
Leeming, D. J.
中科院分区：
文献类型：
--
作者：
Kristensen, J. H.;Larsen, L.;Leeming, D. J.
目的：弹性蛋白是肺部的一种特征蛋白。基质金属蛋白酶-7 （MMP-7）在肺防御机制和降解弹性蛋白中起重要作用。然而，在肺部疾病患者中，关于弹性蛋白降解的MMP-7活性从未被血清学量化。因此，开发了一种定量测定MMP-7产生的弹性蛋白片段（ELM7）的方法，以研究MMP-7产生的弹性蛋白降解在肺部疾病（如特发性肺纤维化（IPF）和肺癌）中的作用。设计和方法：针对弹性蛋白上精心挑选的8个MMP-7切割位点，制备单克隆抗体（mABs）。在鉴定和验证单克隆抗体后，选择一个靶向ELM7片段的单克隆抗体。在诊断为IPF的患者（n = 123，基线样本，CTgov regg）的血清样本中评估ELM7片段水平。NCT00786201)和肺癌（n = 40），并与年龄和性别匹配的对照组进行比较。结果：ELM7实验对体外MMP-7降解弹性蛋白和ELM7新表位具有特异性，但对其他MMP-7衍生的弹性蛋白片段没有特异性。与对照组相比，血清ELM7水平在IPF （113%, p < 0.0001）和肺癌（96%,p < 0.0001）中显著升高。结论：血清中mmp -7产生的弹性蛋白片段可定量表达，并可反映几种重要肺部疾病的病理性肺组织转换。(C) 2015加拿大临床化学学会。Elsevier Inc.出版。版权所有。
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. (C) 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.