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Pericytes contribut...
Pericytes contribute to airway remodeling in a mouse model of chronic allergic asthma
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Johnson, Jill R. (author)
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- Folestad, Erika (author)
- Karolinska Institutet
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Rowley, Jessica E. (author)
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Noll, Elisa M. (author)
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Walker, Simone A. (author)
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Lloyd, Clare M. (author)
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Rankin, Sara M. (author)
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- Pietras, Kristian (author)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine
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- Eriksson, Ulf (author)
- Karolinska Institutet
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- Fuxe, Jonas (author)
- Karolinska Institutet
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(creator_code:org_t)
- American Physiological Society, 2015
- 2015
- English.
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In: American Journal of Physiology: Lung Cellular and Molecular Physiology. - : American Physiological Society. - 1522-1504 .- 1040-0605. ; 308:7, s. 658-671
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Keyword
- asthma
- house dust mite
- airway hyperresponsiveness
- pericyte
- remodeling
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Johnson, Jill R.
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Folestad, Erika
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Rowley, Jessica ...
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Noll, Elisa M.
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Walker, Simone A ...
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Lloyd, Clare M.
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show more...
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Rankin, Sara M.
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Pietras, Kristia ...
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Eriksson, Ulf
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Fuxe, Jonas
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Physiology
- Articles in the publication
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American Journal ...
- By the university
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Lund University
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Karolinska Institutet