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Cited by 65Protease and Inhibitor MechanismsInterstitial Lung Diseases and Idiopathic Pulmonary FibrosisChronic Obstructive Pulmonary Disease (COPD) Research

Measurement of MMP‐9 and ‐12 degraded elastin (ELM) provides unique information on lung tissue degradation

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Skjøt-Arkil, Helene, Clausen, Rikke E, Nguyen, Quoc Hai Trieu, Wang, Yaguo, Zheng, Qinlong, Martinez, Fernando J, Hogaboam, Cory M, Han, Meilan +5 more·2012·BMC Pulmonary Medicine
DOI 10.1186/1471-2466-12-34PMC PMC3515477
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Abstract

BACKGROUND: Elastin 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. METHODS: Elastin 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). RESULTS: The 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. CONCLUSIONS: MMP-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.

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  • Elastic fibres are formed from soluble tropoelastin molecules via cross-linking, generating an amorphous, insoluble and stabilized polymeric structure that confers elasticity to the skin.

    “In resume, elastic fibres are formed from several soluble tropoelastin molecules, an elastin precursor in its monomeric form via cross-linking, and generate an amorphous, insoluble and stabilized polymeric structure that confers elasticity to the skin [33, 35, 37, 45, 46].”

    From Elastin structure and its involvement in skin photoageing (2017) · cites this paper as [33]

    The Background (page unavailable) says that soluble tropoelastin molecules are linked into an insoluble, durable cross-linked array, with cross-links that stabilize elastin and are essential for elasticity. It also identifies elastin as important to skin, but does not describe the resulting structure as amorphous or explicitly state that it confers elasticity to skin. (LLM, conf=0.84)

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Cited by

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Authors
Skjøt-Arkil, H., Clausen, R. E., Nguyen, Q. H. T., Wang, Y., Zheng, Q., Martinez, F. J., Hogaboam, C. M., Han, M., Klickstein, L. B., Larsen, M. R., Nawrocki, A., Leeming, D. J., & Karsdal, M. A.
Affiliations
  • Nordic Bioscience (Denmark) (DK)
  • University of Michigan (US)
  • University of Southern Denmark (DK)
ORCID
Venue
BMC Pulmonary Medicine
Publisher
Springer Science and Business Media LLC
Published
2012-07-20
Volume
12
Issue
1
Pages
34-34
ISSN
1471-2466 (ISSN-L)
DOI
10.1186/1471-2466-12-34
PMC
PMC3515477
OpenAlex
W2056160941
Cited by
65
References
0
Citations by year
2026: 4 · 2025: 4 · 2024: 2 · 2023: 5 · 2022: 3 · 2021: 7 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 7 · 2016: 3 · 2015: 11 · 2014: 8 · 2013: 4
FWCI
2.44
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Pulmonary Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
Funders
  • Louisiana Transportation Research Center
  • National Heart, Lung, and Blood Institute
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
Keywords
elastin degradation, MMP-9, matrix metalloproteinase-12, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, serum biomarkers, monoclonal antibodies, diagnostic biomarkers
MeSH terms
Amino Acid Sequence, Animals, Antibodies, Monoclonal, Epitopes, Elastin, Enzyme-Linked Immunosorbent Assay, Humans, Mice, Inbred BALB C, Molecular Sequence Data, Sensitivity and Specificity, Time Factors, Biomarkers, Case-Control Studies, Matrix Metalloproteinase 9, Pulmonary Disease, Chronic Obstructive, Mice, Matrix Metalloproteinase 12, Idiopathic Pulmonary Fibrosis, In Vitro Techniques

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