Yuhui Ouyang1, Masanori Miyata1, Kyosuke Hatsushika1, Yuko Ohnuma2, Ryohei Katoh3, Hideoki Ogawa4, Ko Okumura4, Keisuke Masuyama5, Atsuhito Nakao6. 1. Department of Immunology,; Department of Otorhinolaryngology, Head and Neck Surgery. 2. Department of Immunology. 3. Department of Human Pathology, University of Yamanashi Faculty of Medicine, Yamanashi. 4. Atopy Research Center, Juntendo University School of Medicine, Tokyo, Japan. 5. Department of Otorhinolaryngology, Head and Neck Surgery. 6. Department of Immunology,; Atopy Research Center, Juntendo University School of Medicine, Tokyo, Japan.. Electronic address: anakao@yamanashi.ac.jp.
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.
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: Elizabeth L Kramer; William D Hardie; Satish K Madala; Cynthia Davidson; John P Clancy Journal: Am J Physiol Lung Cell Mol Physiol Date: 2018-06-07 Impact factor: 5.464
Authors: Surendran Thavagnanam; Jeremy C Parker; Michael E McBrien; Grzegorz Skibinski; Michael D Shields; Liam G Heaney Journal: PLoS One Date: 2014-01-27 Impact factor: 3.240
Authors: Seok Hyun Cho; Sun Young Oh; Andrew P Lane; Joan Lee; Min-Hee Oh; Seakwoo Lee; Tao Zheng; Zhou Zhu Journal: PLoS One Date: 2014-08-04 Impact factor: 3.240