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

Johnson JR, Folestad E, Rowley JE, Noll EM, Walker SA, Lloyd CM, Rankin SM, Pietras K, Eriksson U, Fuxe J - Am. J. Physiol. Lung Cell Mol. Physiol. (2015)

Bottom Line: Unexpectedly, we found that pharmacological inhibition of PDGFRβ signaling in the context of chronic aeroallergen exposure led to exacerbated lung dysfunction and airway smooth muscle thickening.This process was exacerbated in animals treated with CP-673451.The results indicate that perturbed PDGF-BB/PDGFRβ signaling and pericyte accumulation in the airway wall may contribute to airway remodeling in chronic allergic asthma.

View Article: PubMed Central - PubMed

Affiliation: Department 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.

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A: qPCR analysis of PDGF-BB and PDGFRβ mRNA expression in whole-lung lysates from saline and HDM-exposed mice (i.n. 5 days/wk for 5 wk); n = 5 representative of 2 independent experiments. ELISA analysis of PDGF-BB expression in BAL supernatants (B) and immunoblotting for PDGF-BB protein expression (C) in whole-lung lysates from saline and HDM-exposed mice (i.n. 5 days/wk for 5 wk); n = 5–6 (ELISA) and n = 3 (immunoblotting) per group, representative of 2 independent experiments. The immunoblot shown in C presents representative lanes for saline and HDM-exposed mice from 3 replicates per group run on the same gel. D: quantification of PDGF-BB expression assessed by immunoblotting in whole lung homogenates from saline and HDM-exposed mice. *P < 0.05, **P < 0.01.
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Figure 8: A: qPCR analysis of PDGF-BB and PDGFRβ mRNA expression in whole-lung lysates from saline and HDM-exposed mice (i.n. 5 days/wk for 5 wk); n = 5 representative of 2 independent experiments. ELISA analysis of PDGF-BB expression in BAL supernatants (B) and immunoblotting for PDGF-BB protein expression (C) in whole-lung lysates from saline and HDM-exposed mice (i.n. 5 days/wk for 5 wk); n = 5–6 (ELISA) and n = 3 (immunoblotting) per group, representative of 2 independent experiments. The immunoblot shown in C presents representative lanes for saline and HDM-exposed mice from 3 replicates per group run on the same gel. D: quantification of PDGF-BB expression assessed by immunoblotting in whole lung homogenates from saline and HDM-exposed mice. *P < 0.05, **P < 0.01.

Mentions: We next assessed the expression of PDGF-BB and PDGFRβ in the lungs of mice exposed to saline or HDM on the mRNA and protein levels. qPCR analysis of PDGF-BB and PDGFRβ expression in the lung revealed no changes in the expression of these genes after 5 wk of HDM compared with saline mice (Fig. 8A). ELISA performed on BAL supernatants revealed significantly less PDGF-BB expression in the airways of mice exposed to HDM for 3 or 5 wk compared with control mice (Fig. 8B). Immunoblotting analysis showed unaltered levels of the PDGF-BB precursor in lungs from HDM mice vs. saline mice (Fig. 8C). However, a significant decrease in the cleaved, active form of PDGF-BB was found in HDM-exposed mice (Fig. 8D). In line with this, we found that PDGFRβ signaling was reduced in the lungs of mice exposed to HDM for 3 wk and severely compromised after 5 wk (Fig. 8E).


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

Johnson JR, Folestad E, Rowley JE, Noll EM, Walker SA, Lloyd CM, Rankin SM, Pietras K, Eriksson U, Fuxe J - Am. J. Physiol. Lung Cell Mol. Physiol. (2015)

A: qPCR analysis of PDGF-BB and PDGFRβ mRNA expression in whole-lung lysates from saline and HDM-exposed mice (i.n. 5 days/wk for 5 wk); n = 5 representative of 2 independent experiments. ELISA analysis of PDGF-BB expression in BAL supernatants (B) and immunoblotting for PDGF-BB protein expression (C) in whole-lung lysates from saline and HDM-exposed mice (i.n. 5 days/wk for 5 wk); n = 5–6 (ELISA) and n = 3 (immunoblotting) per group, representative of 2 independent experiments. The immunoblot shown in C presents representative lanes for saline and HDM-exposed mice from 3 replicates per group run on the same gel. D: quantification of PDGF-BB expression assessed by immunoblotting in whole lung homogenates from saline and HDM-exposed mice. *P < 0.05, **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 8: A: qPCR analysis of PDGF-BB and PDGFRβ mRNA expression in whole-lung lysates from saline and HDM-exposed mice (i.n. 5 days/wk for 5 wk); n = 5 representative of 2 independent experiments. ELISA analysis of PDGF-BB expression in BAL supernatants (B) and immunoblotting for PDGF-BB protein expression (C) in whole-lung lysates from saline and HDM-exposed mice (i.n. 5 days/wk for 5 wk); n = 5–6 (ELISA) and n = 3 (immunoblotting) per group, representative of 2 independent experiments. The immunoblot shown in C presents representative lanes for saline and HDM-exposed mice from 3 replicates per group run on the same gel. D: quantification of PDGF-BB expression assessed by immunoblotting in whole lung homogenates from saline and HDM-exposed mice. *P < 0.05, **P < 0.01.
Mentions: We next assessed the expression of PDGF-BB and PDGFRβ in the lungs of mice exposed to saline or HDM on the mRNA and protein levels. qPCR analysis of PDGF-BB and PDGFRβ expression in the lung revealed no changes in the expression of these genes after 5 wk of HDM compared with saline mice (Fig. 8A). ELISA performed on BAL supernatants revealed significantly less PDGF-BB expression in the airways of mice exposed to HDM for 3 or 5 wk compared with control mice (Fig. 8B). Immunoblotting analysis showed unaltered levels of the PDGF-BB precursor in lungs from HDM mice vs. saline mice (Fig. 8C). However, a significant decrease in the cleaved, active form of PDGF-BB was found in HDM-exposed mice (Fig. 8D). In line with this, we found that PDGFRβ signaling was reduced in the lungs of mice exposed to HDM for 3 wk and severely compromised after 5 wk (Fig. 8E).

Bottom Line: Unexpectedly, we found that pharmacological inhibition of PDGFRβ signaling in the context of chronic aeroallergen exposure led to exacerbated lung dysfunction and airway smooth muscle thickening.This process was exacerbated in animals treated with CP-673451.The results indicate that perturbed PDGF-BB/PDGFRβ signaling and pericyte accumulation in the airway wall may contribute to airway remodeling in chronic allergic asthma.

View Article: PubMed Central - PubMed

Affiliation: Department 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.

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Related in: MedlinePlus