title: Airway fibroblasts exhibit a synthetic phenotype in severe asthma.
abstract: 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.
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, National Jewish Medical and Research Center, Denver, Colo, USA. cclewis@itsa.ucsf.edu
authors.forename: Christina C
authors.initials: CC
authors.lastname: Lewis
authors.forename: Hong Wei
authors.initials: HW
authors.lastname: Chu
authors.forename: Jay Y
authors.initials: JY
authors.lastname: Westcott
authors.forename: Alan
authors.initials: A
authors.lastname: Tucker
authors.forename: Esther L
authors.initials: EL
authors.lastname: Langmack
authors.forename: E Rand
authors.initials: ER
authors.lastname: Sutherland
authors.forename: Monica
authors.initials: M
authors.lastname: Kraft
mesh_terms: 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
chemical_list: D010982:Platelet-Derived Growth Factor; D011347:Procollagen; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D017479:Receptors, Platelet-Derived Growth Factor