Osteopontin induces airway remodeling and lung fibroblast activation in a murine model of asthma

Martin Kohan, Raphael Breuer, Neville Berkman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Airway remodeling is a central feature of asthma; however, the mechanisms underlying its development have not been fully elucidated. We have demonstrated that osteopontin, an inflammatory cytokine and an extracellular matrix glycoprotein with profibrotic properties, is up-regulated in a murine model of allergen-induced airway remodeling. In the present study, we determined whether osteopontin plays a functional role in airway remodeling. Osteopontin (OPN)-deficient (OPN-/-) and wild-type mice were sensitized and exposed to inhaled ovalbumin (OVA) or saline for 5 weeks. Collagen production, peribronchial smooth muscle area, mucus-producing cell number, and bronchoalveolar cell counts were assessed. The functional behavior and phenotype of lung fibroblasts from OVA-treated OPN-/- and from wild-type mice were studied using ex vivo cultures. OVA-treated OPN-/- mice exhibited reduced lung collagen content, smooth muscle area, mucus-producing cells, and inflammatory cell accumulation as compared with wild-type mice. Reducedmatrix metalloproteinase-2 activity and expression of transforming growth factor-β1 and vascular endothelial growth factor were observed in OVA-treated OPN-/- mice. Lung fibroblasts from OVA-treated OPN -/- mice showed reduced proliferation, migration, collagen deposition, and α-smooth muscle actin expression in comparison with OVA-treated wild-type lung fibroblasts. Thus, OPN is key for the development of allergen-induced airway remodeling in mice. In response to allergen, OPN induces the switching of lung fibroblasts to a pro-fibrogenic myofibroblast phenotype.

Original languageAmerican English
Pages (from-to)290-296
Number of pages7
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume41
Issue number3
DOIs
StatePublished - 1 Sep 2009
Externally publishedYes

Keywords

  • Airway remodeling
  • Fibroblast
  • Mouse model
  • Myofibroblast
  • Osteopontin

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