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Matrilysin expression and function in airway epithelium

S E Dunsmore1, U K Saarialho-Kere, J D Roby

  • 1Department of Medicine (Dermatology), Washington University School of Medicine, St. Louis, Missouri 63110, USA.

The Journal of Clinical Investigation
|October 14, 1998
PubMed
Summary

Matrilysin, a lung enzyme, is crucial for airway repair after injury. Blocking matrilysin significantly hinders epithelial cell migration and lung tissue reepithelialization.

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Area of Science:

  • Pulmonary Medicine
  • Molecular Biology
  • Biochemistry

Background:

  • Matrilysin is a matrix metalloproteinase.
  • Its role in lung injury and repair is not fully understood.

Purpose of the Study:

  • To investigate the expression and function of matrilysin in normal and injured lung epithelium.
  • To determine matrilysin's role in airway epithelial cell migration and reepithelialization.

Main Methods:

  • Immunohistochemistry to detect matrilysin expression in human and mouse lung tissue.
  • Analysis of matrilysin expression in cystic fibrosis and wounded trachea.
  • Inhibition studies using hydroxamate inhibitors.
  • Studies in matrilysin-null mice.

Main Results:

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  • Matrilysin is constitutively expressed in normal lung airways and peribronchial glands.
  • Matrilysin expression is upregulated in airway epithelial cells and induced in alveolar type II cells in cystic fibrosis.
  • Other matrix metalloproteinases are not expressed by lung epithelium.
  • Matrilysin expression increases in migrating airway epithelial cells in wounded trachea.
  • Inhibition of matrilysin significantly reduces epithelial migration and reepithelialization in both human and mouse models.
  • Matrilysin is secreted lumenally and basally by lung epithelium.

Conclusions:

  • Matrilysin plays a critical role in lung injury repair, particularly in facilitating reepithelialization.
  • Its constitutive expression in conducting airways and upregulation after injury suggest multifaceted functions in lung homeostasis and response to damage.
  • Targeting matrilysin may offer therapeutic potential for lung diseases involving impaired repair mechanisms.