title: Basal expression of bone morphogenetic protein receptor is reduced in mild asthma.
abstract: BACKGROUND
  Despite increasing recognition of bone morphogenetic protein (BMP) signaling in tissue remodeling, the expression pattern of ligands and signaling pathways remain undefined in the asthmatic airway.
  
  
  OBJECTIVE
  To determine expression of BMP ligands (BMP-2, BMP-4, and BMP-7) and type I and type II receptors (ALK-2, ALK-3, ALK-6, and BMPRII) as well as evidence for activation of BMP signaling via detection of phosphorylated Smad1/5 (pSmad1/5) expression in asthmatic airways at baseline (compared with nonasthmatic controls), and after allergen challenge.
  
  
  METHODS
  Bronchial biopsies were obtained from 6 nonasthmatic control volunteers, and 15 atopic patients with asthma (median age, 25 yr; median FEV(1)% predicted, 97%) at baseline, then at 24 hours and 7 days after allergen challenge. Expression of BMP ligands, receptors, and signaling was analyzed using immunohistochemistry.
  
  
  RESULTS
  BMP ligand expression did not differ between asthmatic and control airways at baseline. Compared with the normal airway, there was significant down-regulation of ALK-2 (P = 0.001), ALK-6 (P = 0.0009), and BMPRII (P = 0.009) expression in asthma. Allergen challenge was associated with marked and sustained up-regulation of BMP-7 in airway epithelium (P = 0.017) and infiltrating inflammatory cells (P = 0.071) (predominantly in eosinophils, but also CD4(+) T cells, mast cells, and macrophages). Up-regulation of pSmad1/5 expression (P = 0.031), ALK-2 (P = 0.002), and ALK-6 (P < 0.001) was observed indicating active signaling.
  
  
  CONCLUSIONS
  BMP receptor expression is down-regulated in the asthmatic airway, which may impede repair responses. Allergen provocation increases expression of the regulatory ligand BMP-7, activates BMP signaling, and increases receptor expression, all of which may contribute to repair and control of inflammation.
authors.affiliation: Emeritus Professor of Allergy and Clinical Immunology, Sir Alexander Fleming Building, Leukocyte Biology Section, Imperial College, South Kensington Campus, London, SW7 2AZ UK.
authors.forename: Harsha H
authors.initials: HH
authors.lastname: Kariyawasam
authors.forename: Georgina
authors.initials: G
authors.lastname: Xanthou
authors.forename: Julia
authors.initials: J
authors.lastname: Barkans
authors.forename: Maxine
authors.initials: M
authors.lastname: Aizen
authors.forename: A Barry
authors.initials: AB
authors.lastname: Kay
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Robinson
mesh_terms: D030201:Activin Receptors, Type I / Q000378:metabolism*; D000328:Adult; D001249:Asthma / Q000378:metabolism / Q000503:physiopathology*; D001706:Biopsy; D055419:Bone Morphogenetic Protein 7; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism*; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism*; D001985:Bronchial Provocation Tests; D016022:Case-Control Studies; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C425423:ACVR1 protein, human; D030201:Activin Receptors, Type I; C498214:BMPR1B protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II