Matrix Metalloproteinases and Their Inhibitors in Chronic Obstructive Pulmonary Disease

Arch Immunol Ther Exp (Warsz). 2016 Jun;64(3):177-93. doi: 10.1007/s00005-015-0375-5. Epub 2015 Nov 26.

Abstract

Chronic obstructive pulmonary disease (COPD) is characterised by irreversible airflow limitation associated with chronic inflammation. Matrix metalloproteinases (MMPs) are proteolytic enzymes that contribute to the inflammatory response in COPD and degrade extracellular matrix components. Their enzymatic activity is inhibited by a four-member family of tissue inhibitors of metalloproteinases (TIMPs). In COPD, the MMP/TIMP network, mainly MMP-9, has been repeatedly observed to be dysregulated at both the local (lung) and systemic levels. Here, we review the findings reported in numerous cross-sectional studies with our primary focus on longitudinal observations in human COPD studies. The data from longitudinal prospective studies on the MMP/TIMP network may lead to the introduction of novel prognostic biomarkers into clinical management of COPD. We address the relationship between the systemic and local lung MMP/TIMP network in COPD patients and briefly describe the involvement of microRNAs. Finally, the role of the MMP/TIMP network in COPD treatment is discussed.

Keywords: Biomarker; Chronic obstructive pulmonary disease; Local and systemic response; Matrix metalloproteinases; MicroRNAs; Tissue inhibitors of metalloproteinases.

Publication types

  • Review

MeSH terms

  • Biomarkers / metabolism
  • Cross-Sectional Studies
  • Gene Expression Regulation, Enzymologic*
  • Humans
  • Inflammation
  • Lung / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinases / metabolism*
  • MicroRNAs / metabolism
  • Phenotype
  • Prognosis
  • Pulmonary Disease, Chronic Obstructive / enzymology*
  • Tissue Inhibitor of Metalloproteinases / metabolism*

Substances

  • Biomarkers
  • MicroRNAs
  • Tissue Inhibitor of Metalloproteinases
  • Matrix Metalloproteinases
  • MMP9 protein, human
  • Matrix Metalloproteinase 9