Pericytes contribute to airway remodeling in a mouse model of chronic allergic asthma

Research output: Contribution to journalArticle

Abstract

Myofibroblast accumulation, subepithelial fibrosis, and vascular remodeling are complicating features of chronic asthma, but the mechanisms are not clear. Platelet-derived growth factors (PDGFs) regulate the fate and function of various mesenchymal cells and have been implicated as mediators of lung fibrosis. However, it is not known whether PDGF-BB signaling via PDGFR beta, which is critical for the recruitment of pericytes to blood vessels, plays a role in airway remodeling in chronic asthma. In the present study, we used a selective PDGFR beta inhibitor (CP-673451) to investigate the role of PDGFR beta signaling in the development of airway remodeling and lung dysfunction in an established mouse model of house dust mite-induced chronic allergic asthma. Unexpectedly, we found that pharmacological inhibition of PDGFR beta signaling in the context of chronic aeroallergen exposure led to exacerbated lung dysfunction and airway smooth muscle thickening. Further studies revealed that the inflammatory response to aeroallergen challenge in mice was associated with decreased PDGF-BB expression and the loss of pericytes from the airway microvasculature. In parallel, cells positive for pericyte markers accumulated in the subepithelial region of chronically inflamed airways. This process was exacerbated in animals treated with CP-673451. The results indicate that perturbed PDGF-BB/PDGFR beta signaling and pericyte accumulation in the airway wall may contribute to airway remodeling in chronic allergic asthma.

Details

Authors
  • Jill R. Johnson
  • Erika Folestad
  • Jessica E. Rowley
  • Elisa M. Noll
  • Simone A. Walker
  • Clare M. Lloyd
  • Sara M. Rankin
  • Kristian Pietras
  • Ulf Eriksson
  • Jonas Fuxe
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Physiology

Keywords

  • asthma, house dust mite, airway hyperresponsiveness, pericyte, remodeling
Original languageEnglish
Pages (from-to)L658-L671
JournalAmerican Journal of Physiology: Lung Cellular and Molecular Physiology
Volume308
Issue number7
Publication statusPublished - 2015
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Experimental oncology (013031110)