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

Jill R Johnson1, Erika Folestad2, Jessica E Rowley3

  • 1Department of Medical Biochemistry and Biophysics, Matrix Division, Division of Vascular Biology, Karolinska Institutet, Stockholm, Sweden; Leukocyte Biology Section, National Heart and Lung Institute, Sir Alexander Fleming Building, Imperial College London, London, United Kingdom; and jill.johnson@imperial.ac.uk.

American Journal of Physiology. Lung Cellular and Molecular Physiology
|February 1, 2015
PubMed

Insights

In chronic asthma, inhibiting PDGFRβ signaling worsened lung dysfunction and airway thickening. This suggests PDGF-BB/PDGFRβ signaling and pericyte accumulation contribute to airway remodeling.

Area of Science:

  • Pulmonary Medicine
  • Immunology
  • Cell Biology

Background:

  • Chronic asthma involves myofibroblast accumulation, subepithelial fibrosis, and vascular remodeling, with unclear mechanisms.
  • Platelet-derived growth factors (PDGFs) are implicated in lung fibrosis, but their role in asthma airway remodeling is unknown.
  • PDGF-BB signaling via PDGFRβ is crucial for pericyte recruitment, but its function in asthma is not established.

Purpose of the Study:

  • To investigate the role of PDGFRβ signaling in airway remodeling and lung dysfunction in a mouse model of chronic allergic asthma.
  • To determine if inhibiting PDGFRβ signaling affects airway remodeling and lung function in established asthma.

Main Methods:

  • Utilized a selective PDGFRβ inhibitor (CP-673451) in a house dust mite-induced chronic allergic asthma mouse model.
  • Assessed lung dysfunction, airway smooth muscle thickness, and inflammatory responses.
  • Examined PDGF-BB expression, pericyte markers, and their localization in airway tissues.

Main Results:

  • Unexpectedly, PDGFRβ inhibition exacerbated lung dysfunction and airway smooth muscle thickening in asthmatic mice.
  • Aeroallergen challenge led to decreased PDGF-BB expression and pericyte loss from airway microvasculature.
  • Pericyte marker-positive cells accumulated in the subepithelial region, a process worsened by PDGFRβ inhibition.

Conclusions:

  • Perturbed PDGF-BB/PDGFRβ signaling contributes to airway remodeling in chronic allergic asthma.
  • Pericyte accumulation in the airway wall is linked to asthma pathogenesis.
  • Targeting PDGFRβ signaling may have complex effects on asthma progression.
Keywords:
airway hyperresponsivenessasthmahouse dust mitepericyteremodeling

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