TGF-β Signaling May Play a Role in the Development of Goblet Cell Hyperplasia in a Mouse Model of Allergic Rhinitis
ABSTRACT: Background: Transforming growth factor-p (TGF-β) levels are elevated in the nasal mucosa in allergic rhinitis. However, because TGF-β is secreted extracellulary in latent complexes, it remains unclear whether the local TGF-β expression actually drives active signaling and affects the path...
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Format: | Article |
Language: | English |
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Elsevier
2010-01-01
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Series: | Allergology International |
Online Access: | http://www.sciencedirect.com/science/article/pii/S1323893015306419 |
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author | Yuhui Ouyang Masanori Miyata Kyosuke Hatsushika Yuko Ohnuma Ryohei Katoh Hideoki Ogawa Ko Okumura Keisuke Masuyama Atsuhito Nakao |
author_facet | Yuhui Ouyang Masanori Miyata Kyosuke Hatsushika Yuko Ohnuma Ryohei Katoh Hideoki Ogawa Ko Okumura Keisuke Masuyama Atsuhito Nakao |
author_sort | Yuhui Ouyang |
collection | DOAJ |
description | ABSTRACT: Background: Transforming growth factor-p (TGF-β) levels are elevated in the nasal mucosa in allergic rhinitis. However, because TGF-β is secreted extracellulary in latent complexes, it remains unclear whether the local TGF-β expression actually drives active signaling and affects the pathophysiology of allergic rhinitis. The objective of this study is to investigate whether TGF-β 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-β 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-β 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-β signaling is activated in epithelial cells in the nasal mucosa in allergic rhinitis and may contribute to the development of goblet cell hyperplasia. KEY WORDS: allergic rhinitis, epithelial cells, Smad, TGF-p |
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id | doaj.art-03eebd8b4b104c0c88d726a002f8cadd |
institution | Directory Open Access Journal |
issn | 1323-8930 |
language | English |
last_indexed | 2024-04-13T05:29:55Z |
publishDate | 2010-01-01 |
publisher | Elsevier |
record_format | Article |
series | Allergology International |
spelling | doaj.art-03eebd8b4b104c0c88d726a002f8cadd2022-12-22T03:00:28ZengElsevierAllergology International1323-89302010-01-01593313319TGF-β Signaling May Play a Role in the Development of Goblet Cell Hyperplasia in a Mouse Model of Allergic RhinitisYuhui Ouyang0Masanori Miyata1Kyosuke Hatsushika2Yuko Ohnuma3Ryohei Katoh4Hideoki Ogawa5Ko Okumura6Keisuke Masuyama7Atsuhito Nakao8Department of Immunology,; Department of Otorhinolaryngology, Head and Neck Surgery,Department of Immunology,; Department of Otorhinolaryngology, Head and Neck Surgery,Department of Immunology,; Department of Otorhinolaryngology, Head and Neck Surgery,Department of Immunology,Department of Human Pathology, University of Yamanashi Faculty of Medicine, YamanashiAtopy Research Center, Juntendo University School of Medicine, Tokyo, Japan.Atopy Research Center, Juntendo University School of Medicine, Tokyo, Japan.Department of Otorhinolaryngology, Head and Neck Surgery,Department of Immunology,; Atopy Research Center, Juntendo University School of Medicine, Tokyo, Japan.; Correspondence: Atsuhito Nakao, Department of Immunology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409−3898, Japan.ABSTRACT: Background: Transforming growth factor-p (TGF-β) levels are elevated in the nasal mucosa in allergic rhinitis. However, because TGF-β is secreted extracellulary in latent complexes, it remains unclear whether the local TGF-β expression actually drives active signaling and affects the pathophysiology of allergic rhinitis. The objective of this study is to investigate whether TGF-β 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-β 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-β 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-β signaling is activated in epithelial cells in the nasal mucosa in allergic rhinitis and may contribute to the development of goblet cell hyperplasia. KEY WORDS: allergic rhinitis, epithelial cells, Smad, TGF-phttp://www.sciencedirect.com/science/article/pii/S1323893015306419 |
spellingShingle | Yuhui Ouyang Masanori Miyata Kyosuke Hatsushika Yuko Ohnuma Ryohei Katoh Hideoki Ogawa Ko Okumura Keisuke Masuyama Atsuhito Nakao TGF-β Signaling May Play a Role in the Development of Goblet Cell Hyperplasia in a Mouse Model of Allergic Rhinitis Allergology International |
title | TGF-β Signaling May Play a Role in the Development of Goblet Cell Hyperplasia in a Mouse Model of Allergic Rhinitis |
title_full | TGF-β Signaling May Play a Role in the Development of Goblet Cell Hyperplasia in a Mouse Model of Allergic Rhinitis |
title_fullStr | TGF-β Signaling May Play a Role in the Development of Goblet Cell Hyperplasia in a Mouse Model of Allergic Rhinitis |
title_full_unstemmed | TGF-β Signaling May Play a Role in the Development of Goblet Cell Hyperplasia in a Mouse Model of Allergic Rhinitis |
title_short | TGF-β Signaling May Play a Role in the Development of Goblet Cell Hyperplasia in a Mouse Model of Allergic Rhinitis |
title_sort | tgf β signaling may play a role in the development of goblet cell hyperplasia in a mouse model of allergic rhinitis |
url | http://www.sciencedirect.com/science/article/pii/S1323893015306419 |
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