Matrix metalloproteinase 12 silencing: a therapeutic approach to treat pathological lung tissue remodeling?

Pulm Pharmacol Ther. 2009 Aug;22(4):267-78. doi: 10.1016/j.pupt.2009.03.001. Epub 2009 Mar 25.


Among the large matrix metalloproteinases (MMPs) family, MMP-12, also referred to as macrophage elastase, plays a significant role in chronic pulmonary pathologies characterized by an intense tissue remodeling such as asthma and COPD. This review will summarize knowledge about MMP-12 structure, functions and mechanisms of activation and regulation, including potential MMP-12 modulation by microRNA. As MMP-12 is involved in many tissue remodeling diseases, efforts have been made to develop specific synthetic inhibitors. However, at this time, very few chemical inhibitors have proved to be efficient and specific to a particular MMP. The relevance of silencing MMP-12 by RNA interference is highlighted. The specificity of this approach using siRNA or shRNA and the strategies to deliver these molecules in the lung are discussed.

Publication types

  • Review

MeSH terms

  • Animals
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Gene Expression Regulation, Enzymologic / genetics
  • Gene Expression Regulation, Enzymologic / physiology
  • Gene Silencing*
  • Humans
  • Lung / pathology
  • Lung Diseases / pathology*
  • Lung Diseases / therapy*
  • Matrix Metalloproteinase 12 / biosynthesis
  • Matrix Metalloproteinase 12 / genetics*
  • Matrix Metalloproteinase 12 / physiology
  • Matrix Metalloproteinase Inhibitors
  • RNA Interference


  • Enzyme Inhibitors
  • Matrix Metalloproteinase Inhibitors
  • Matrix Metalloproteinase 12