Revisiting matrix metalloproteinase 12: its role in pathophysiology of asthma and related pulmonary diseases

Curr Opin Pulm Med. 2021 Jan;27(1):54-60. doi: 10.1097/MCP.0000000000000743.

Abstract

Purpose of review: Matrix metalloproteinases (MMPs) are a family of over 20 zinc-dependent proteases with different biological and pathological activities, and many have been implicated in several diseases. Although nonselective MMP inhibitors are known to induce serious side-effects, targeting individual MMPs may offer a safer therapeutic potential for several diseases. Hence, we provide a concise overview on MMP-12, given its association with pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, and other progressive pulmonary fibrosis (PPF), which may also occur in coronavirus disease 2019.

Recent findings: In asthma, COPD, and PPF, increased MMP-12 levels have been associated with inflammation and/or structural changes within the lungs and negatively correlated with functional parameters. Increased pulmonary MMP-12 levels and MMP-12 gene expression have been related to disease severity in asthma and COPD. Targeting MMP-12 showed potential in animal models of pulmonary diseases but human data are still very scarce.

Summary: Although there may be a potential role of MMP-12 in asthma, COPD and PPF, several pathophysiological aspects await elucidation. Targeting MMP-12 may provide further insights into MMP-12 related mechanisms and how this translates into clinical outcomes; this warrants further research.

Publication types

  • Review

MeSH terms

  • Animals
  • Asthma / drug therapy
  • Asthma / enzymology*
  • Asthma / etiology
  • Asthma / physiopathology
  • Biomarkers / metabolism
  • COVID-19 / drug therapy
  • COVID-19 / enzymology*
  • COVID-19 / etiology
  • COVID-19 / physiopathology
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy
  • Idiopathic Pulmonary Fibrosis / enzymology*
  • Idiopathic Pulmonary Fibrosis / etiology
  • Idiopathic Pulmonary Fibrosis / physiopathology
  • Matrix Metalloproteinase 12 / metabolism*
  • Matrix Metalloproteinase Inhibitors / therapeutic use
  • Pulmonary Disease, Chronic Obstructive / drug therapy
  • Pulmonary Disease, Chronic Obstructive / enzymology*
  • Pulmonary Disease, Chronic Obstructive / etiology
  • Pulmonary Disease, Chronic Obstructive / physiopathology

Substances

  • Biomarkers
  • Matrix Metalloproteinase Inhibitors
  • Matrix Metalloproteinase 12