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

Johnson, Jill R.; Folestad, Erika; Rowley, Jessica E.; Noll, Elisa M.; Walker, Simone A.; Lloyd, Clare M.; Rankin, Sara M.; Pietras, Kristian LU ; Eriksson, Ulf and Fuxe, Jonas (2015) In American Journal of Physiology: Lung Cellular and Molecular Physiology 308(7). p.658-671
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
asthma, house dust mite, airway hyperresponsiveness, pericyte, remodeling
in
American Journal of Physiology: Lung Cellular and Molecular Physiology
volume
308
issue
7
pages
658 - 671
publisher
American Physiological Society
external identifiers
  • wos:000352165800007
  • scopus:84926314130
ISSN
1522-1504
DOI
10.1152/ajplung.00286.2014
language
English
LU publication?
yes
id
80fef1a0-fc6a-46c1-be93-bb8172595fde (old id 5402846)
date added to LUP
2015-06-01 09:22:59
date last changed
2017-05-28 03:20:06
@article{80fef1a0-fc6a-46c1-be93-bb8172595fde,
  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.},
  author       = {Johnson, Jill R. and Folestad, Erika and Rowley, Jessica E. and Noll, Elisa M. and Walker, Simone A. and Lloyd, Clare M. and Rankin, Sara M. and Pietras, Kristian and Eriksson, Ulf and Fuxe, Jonas},
  issn         = {1522-1504},
  keyword      = {asthma,house dust mite,airway hyperresponsiveness,pericyte,remodeling},
  language     = {eng},
  number       = {7},
  pages        = {658--671},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Lung Cellular and Molecular Physiology},
  title        = {Pericytes contribute to airway remodeling in a mouse model of chronic allergic asthma},
  url          = {http://dx.doi.org/10.1152/ajplung.00286.2014},
  volume       = {308},
  year         = {2015},
}