title: TGF-beta signaling may play a role in the development of goblet cell hyperplasia in a mouse model of allergic rhinitis.
abstract: BACKGROUND
  Transforming growth factor-beta (TGF-beta) levels are elevated in the nasal mucosa in allergic rhinitis. However, because TGF-beta is secreted extracellulary in latent complexes, it remains unclear whether the local TGF-beta expression actually drives active signaling and affects the pathophysiology of allergic rhinitis. The objective of this study is to investigate whether TGF-beta signaling is activated in allergic rhinitis and plays a role in the pathophysiology of allergic rhinitis.
  
  
  METHODS
  An ovabumin (OVA)-sensitized and -nasally challenged mouse model of allergic rhinitis was established and phosphorylation of Smad2 in the nasal mucosa was examined by immunohistochemistry. In addition, the effects of the pharmacological inhibition of endogenous TGF-beta signaling on the allergic rhinitis model were histologically examined. Furthermore, phosphorylation of Smad2 in the nasal mucosa samples obtained from patients with allergic rhinitis was also evaluated.
  
  
  RESULTS
  In the mouse model of allergic rhinitis, OVA challenge induced phosphorylation of Smad2 predominantly in epithelial cells in the nasal mucosa. In addition, the administration of an inhibitor of TGF-beta type I receptor kinase activity during OVA challenge suppressed goblet cell hyperplasia in the nasal mucosa. Furthermore, phosphorylated Smad2 expression increased in nasal epithelial cells in patients with allergic rhinitis.
  
  
  CONCLUSIONS
  These results suggest that TGF-beta signaling is activated in epithelial cells in the nasal mucosa in allergic rhinitis and may contribute to the development of goblet cell hyperplasia.
authors.affiliation: Department of Immunology,; Department of Otorhinolaryngology, Head and Neck Surgery.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Ouyang
authors.affiliation: Department of Immunology,; Department of Otorhinolaryngology, Head and Neck Surgery.
authors.forename: Masanori
authors.initials: M
authors.lastname: Miyata
authors.affiliation: Department of Immunology,; Department of Otorhinolaryngology, Head and Neck Surgery.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Hatsushika
authors.affiliation: Department of Immunology.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ohnuma
authors.affiliation: Department of Human Pathology, University of Yamanashi Faculty of Medicine, Yamanashi.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Katoh
authors.affiliation: Atopy Research Center, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Atopy Research Center, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Masuyama
authors.affiliation: Department of Immunology,; Atopy Research Center, Juntendo University School of Medicine, Tokyo, Japan.. Electronic address: anakao@yamanashi.ac.jp.
authors.forename: Atsuhito
authors.initials: A
authors.lastname: Nakao
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D020397:Goblet Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D007114:Immunization; D051379:Mice; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology* / Q000378:metabolism; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: C506615:HTS 466284; D011720:Pyrazoles; D011804:Quinolines; D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; D010047:Ovalbumin; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I