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MMP activation peptide detection in biological samples as a diagnostic marker of idiopathic pulmonary fibrosis
Author(s) -
Voeghtly Laura M,
Kaminski Naftali,
Oury Tim D
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.572.11
Subject(s) - proteases , matrix metalloproteinase , idiopathic pulmonary fibrosis , mmp9 , medicine , fibrosis , pulmonary fibrosis , mmp2 , lung , elastase , extracellular matrix , immunology , pathology , downregulation and upregulation , biology , enzyme , microbiology and biotechnology , cancer , metastasis , biochemistry , gene
Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease of unknown etiology. Historically, IPF has been seen as a gradually progressive disease. However some patients with IPF experience acute exacerbations of IPF characterized by a rapid deterioration of lung function and accelerated death. Matrix metalloproteases (MMPs) are a family of proteases that regulate extracellular matrix turnover. Some MMPs have been shown to be upregulated in IPF and these MMPs are thought to directly contribute to disease progression. MMPs are proteases that are subject to inhibition once activated. The inhibited complexes are rapidly cleared preventing accurate biological detection of MMP activation. In contrast, the mechanism of clearance of the activation peptides released from the MMPs is unknown. ELISA experiments show that the activation peptides of MMP2, MMP7, and MMP9 are elevated in the urine of mice with pulmonary fibrosis compared to WT mice and in the urine of human patients with IPF compared to healthy controls. These data suggest that urine detection of MMP activation peptides is feasible and correlates with disease. Because MMP activation contributes to disease initiation and progression, we hypothesize that the accurate detection of the activation of these proteases will be relevant clinically and may allow for earlier detection of disease as well as allow for prediction of acute exacerbations.