title: Extra domain-A fibronectin is necessary for the development of nasal remodeling in chronic allergen-induced rhinitis.
abstract: BACKGROUND
  Extra domain A-containing fibronectin (EDA-FN) is necessary for the development of allergen-induced lower airway fibrosis. The pathogenesis of fibrosis in allergic rhinitis has not been well studied.
  
  
  OBJECTIVE
  To determine whether EDA-fibronectin is necessary for the development of nasal remodeling in a murine model of chronic allergic rhinitis and in human allergic rhinitis.
  
  
  METHODS
  EDA(-/-) and wild-type (WT) C57Bl/6 mice were sensitized intraperitoneally and then challenged with inhaled ovalbumin (OVA) or saline for 2 and 5 weeks. Clinical signs of rhinitis and histological analysis of nasal tissue were evaluated. Immunohistological staining for EDA-FN was performed in human tissue of inferior nasal conchae from patients with allergic rhinitis and controls.
  
  
  RESULTS
  After 2 weeks of allergen exposure, only goblet cell hyperplasia and perivascular eosinophilia were observed. After 5 weeks, goblet cell number, thickening of the subepithelial layer, and extent and area of collagen deposition were increased in the nasal tissue of WT OVA (ovalbumin)-challenged mice as compared with saline controls (P < .0001, P < .0001, P = .018, and P = .03, respectively). Clinical signs of rhinitis were observed only in WT OVA-challenged mice. In the EDA(-/-) mice exposed to OVA, collagen deposition, collagen area, and subepithelial thickness showed no increase and were similar to saline control mice, whereas goblet cell hyperplasia was similar to WT OVA-challenged mice. EDA-FN expression was prominent in inferior conchae from patients with allergic rhinitis but was absent in control patients.
  
  
  CONCLUSIONS
  EDA-containing fibronectin is necessary for the development of nasal tissue fibrotic remodeling process in both murine and human allergic rhinitis.
authors.affiliation: Department of Otolaryngology/Head & Neck Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. drnir@hadassah.org.il
authors.forename: Nir
authors.initials: N
authors.lastname: Hirshoren
authors.forename: Martin
authors.initials: M
authors.lastname: Kohan
authors.forename: Miri
authors.initials: M
authors.lastname: Assayag
authors.forename: Tzahi
authors.initials: T
authors.lastname: Neuman
authors.forename: Fiona
authors.initials: F
authors.lastname: Vernea
authors.forename: Andres
authors.initials: A
authors.lastname: Muro
authors.forename: Ron
authors.initials: R
authors.lastname: Eliashar
authors.forename: Neville
authors.initials: N
authors.lastname: Berkman
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology; D000818:Animals; D003094:Collagen / Q000276:immunology; D004802:Eosinophilia / Q000276:immunology; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000276:immunology*; D020397:Goblet Cells / Q000473:pathology; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology* / Q000473:pathology; D010047:Ovalbumin / Q000276:immunology; D012220:Rhinitis / Q000276:immunology* / Q000473:pathology
chemical_list: D000485:Allergens; D005353:Fibronectins; C574442:extra domain A fibronectin, human; C572454:extra domain A fibronectin, mouse; D010047:Ovalbumin; D003094:Collagen