@article{oai:dmu.repo.nii.ac.jp:00000214, author = {Ota, Mayumi and Nakao, Atsuhito and Sugiyama, Kumiya and Cheng, Gang and Akimoto, Kazumi and Okada, Takenori and Sagara, Hironori}, issue = {1}, journal = {Dokkyo journal of medical sciences}, month = {Mar}, note = {Transforming growth factor-β (TGF-β) is a profibrogenic cytokine that is involved in airway remodeling largely associated with chronic asthma. Accordingly, regulators of TGF-β activity could also play some role in airway remodeling in asthma. In this study, we investigated expression of Smad 7, a major intracellular inhibitor of TGF-β signaling, in the airways of mouse models of acute and chronic asthma. Sensitized, repeatedly (14 days) ovalbumin (OVA)-inhaled BALB/c mice exhibited evidence of airway remodeling including prominent subepithelial fibrosis associated with airway hyperresponsiveness (AHR) and airway inflammation (chronic asthma model) whereas sensitized, shortly OVA-inhaled BALB/c mice showed only AHR and airway inflammation (acute asthma model). Immunohistochemical analysis showed that Smad 7 immunoreactivity in the airways was increased after the development of acute and chronic asthma models and mainly detected in bronchial epithelial cells. Interestingly, Smad 7 immunoreactivity was significantly less in the airways of chronic asthma model than in those of acute asthma model, which was also confirmed by real-time PCR analysis of Smad 7. In consistent with decreased Smad 7 expression in the airways of chronic asthma model, phosphorylation of Smad 2, a marker of active TGF-β signaling, was increased in bronchial epithelial cells of chronic asthma model when compared with acute asthma model. These results suggest that decreased Smad 7 expression and Smad 2 upregulation in bronchial epithelial cells might result in increased TGF-β activity and contribute to the development of airway remodeling seen in chronic asthma., 原著, Original}, pages = {17--26}, title = {Airway Expression of Smad7, a TGF-β-inducible Inhibitory Molecule of TGF-β Signaling, Decreases after Repeated Airway Antigen Challenges}, volume = {31}, year = {2004} }