Airway fibroblasts exhibit a synthetic phenotype in severe asthma.
BACKGROUND
Platelet-derived growth factor (PDGF) may have a significant role in airway remodeling in asthma, because it is a powerful inductor of many airway fibroblast activities such as collagen synthesis.


OBJECTIVE
To determine whether PDGF is a significant contributor to airway remodeling in patients with asthma by enhancing airway fibroblast procollagen I expression.


METHODS
Six normal controls without asthma, 10 subjects with mild to moderate asthma, and 5 subjects with severe asthma underwent bronchoscopy with endobronchial biopsy. Biopsies were placed in Dulbecco modified Eagle medium and fibroblasts cultured in the presence and absence of PDGF isoforms -AA, -BB, and -AB (1, 5, 10, 100 ng/mL) and insulin-like growth factor 1 (100 ng/mL). Fibroblast procollagen I and PDGF receptors (PDGFRs) alpha and beta expression were determined by ELISA.


RESULTS
Platelet-derived growth factor BB significantly enhanced fibroblast procollagen I expression in patients with severe asthma compared with patients with mild/moderate asthma and normal controls. Furthermore, the baseline fibroblast expression of PDGFR-beta was significantly greater in patients with severe asthma compared with the other groups.


CONCLUSIONS
This pilot study suggests that airway fibroblasts from patients with severe asthma exhibit a synthetic phenotype, which may be driven by the overexpression of PDGFR-beta.
Lewis
Christina C
CC
Division of Pulmonary Sciences and Critical Care Medicine, National Jewish Medical and Research Center, Denver, Colo, USA. cclewis@itsa.ucsf.edu
Chu
Hong Wei
HW
Westcott
Jay Y
JY
Tucker
Alan
A
Langmack
Esther L
EL
Sutherland
E Rand
ER
Kraft
Monica
M
D000328:Adult; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D000077214:Becaplermin; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D008297:Male; D010641:Phenotype; D010865:Pilot Projects; D010982:Platelet-Derived Growth Factor / Q000276:immunology / Q000494:pharmacology; D011347:Procollagen / Q000096:biosynthesis; D020574:Proto-Oncogene Proteins c-sis; D017479:Receptors, Platelet-Derived Growth Factor / Q000276:immunology / Q000378:metabolism
D010982:Platelet-Derived Growth Factor; D011347:Procollagen; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D017479:Receptors, Platelet-Derived Growth Factor