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

Author:
  • 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
Publishing year: 2015
Language: English
Pages: 658-671
Publication/Series: American Journal of Physiology: Lung Cellular and Molecular Physiology
Volume: 308
Issue: 7
Document type: Journal article
Publisher: American Physiological Society

Abstract english

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.

Keywords

  • Physiology
  • asthma
  • house dust mite
  • airway hyperresponsiveness
  • pericyte
  • remodeling

Other

Published
  • ISSN: 1522-1504
Kristian Pietras
E-mail: kristian [dot] pietras [at] med [dot] lu [dot] se

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Division of Translational Cancer Research

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Experimental oncology