BMC Pulmonary Medicine | |
Measurement of MMP-9 and -12 degraded elastin (ELM) provides unique information on lung tissue degradation | |
Research Article | |
Martin R Larsen1  Arkadiusz Nawrocki1  Cory M Hogaboam2  Meilan Han2  Fernando J Martinez2  Rikke E Clausen3  Diana J Leeming3  Morten A Karsdal3  Quoc Hai Trieu Nguyen3  Helene Skjøt-Arkil4  Yaguo Wang5  Qinlong Zheng5  Lloyd B Klickstein6  | |
[1] Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark;Division of Pulmonary and Critical Care Medicine and Department of Pathology, University of Michigan, Ann Arbor, MI, USA;Nordic Bioscience A/S, Herlev Hovedgade 207, DK-2730, Herlev, Denmark;Nordic Bioscience A/S, Herlev Hovedgade 207, DK-2730, Herlev, Denmark;Institute of Clinical Research, Odense University Hospital, Odense, Denmark;Nordic Bioscience Beijing, Beijing, China;Novartis Institutes for Biomedical Research, Cambridge, MA, USA; | |
关键词: Elastin; Extracellular matrix remodeling; Biochemical marker; Neoepitope; COPD; IPF; MMP; | |
DOI : 10.1186/1471-2466-12-34 | |
received in 2012-01-03, accepted in 2012-07-03, 发布年份 2012 | |
来源: Springer | |
【 摘 要 】
BackgroundElastin is an essential component of selected connective tissues that provides a unique physiological elasticity. Elastin may be considered a signature protein of lungs where matrix metalloprotease (MMP) -9-and -12, may be considered the signature proteases of the macrophages, which in part are responsible for tissue damage during disease progression. Thus, we hypothesized that a MMP-9/-12 generated fragment of elastin may be a relevant biochemical maker for lung diseases.MethodsElastin fragments were identified by mass-spectrometry and one sequence, generated by MMP-9 and -12 (ELN-441), was selected for monoclonal antibody generation and used in the development of an ELISA. Soluble and insoluble elastin from lung was cleaved in vitro and the time-dependent release of fragments was assessed in the ELN-441 assay. The release of ELN-441 in human serum from patients with chronic obstructive pulmonary disease (COPD) (n = 10) and idiopathic pulmonary fibrosis (IPF) (n = 29) were compared to healthy matched controls (n = 11).ResultsThe sequence ELN-441 was exclusively generated by MMP-9 and -12 and was time-dependently released from soluble lung elastin. ELN-441 levels were 287% higher in patients diagnosed with COPD (p < 0.001) and 124% higher in IPF patients (p < 0.0001) compared with controls. ELN-441 had better diagnostic value in COPD patients (AUC 97%, p = 0.001) than in IPF patients (AUC 90%, p = 0.0001). The odds ratios for differentiating controls from COPD or IPF were 24 [2.06–280] for COPD and 50 [2.64–934] for IPF.ConclusionsMMP-9 and -12 time-dependently released the ELN-441 epitope from elastin. This fragment was elevated in serum from patients with the lung diseases IPF and COPD, however these data needs to be validated in larger clinical settings.
【 授权许可】
CC BY
© Skjøt-Arkil et al.; licensee BioMed Central Ltd. 2012
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO202311094755872ZK.pdf | 852KB | download |
【 参考文献 】
- [1]
- [2]
- [3]
- [4]
- [5]
- [6]
- [7]
- [8]
- [9]
- [10]
- [11]
- [12]
- [13]
- [14]
- [15]
- [16]
- [17]
- [18]
- [19]
- [20]
- [21]
- [22]
- [23]
- [24]
- [25]
- [26]
- [27]
- [28]
- [29]
- [30]
- [31]
- [32]
- [33]
- [34]
- [35]
- [36]
- [37]
- [38]
- [39]
- [40]
- [41]
- [42]
- [43]
- [44]
- [45]
- [46]
- [47]
- [48]
- [49]
- [50]
- [51]
- [52]
- [53]
- [54]