Inhibitory Effects of Resveratrol on Airway Remodeling by Transforming Growth Factor-β/Smad Signaling Pathway in Chronic Asthma Model.
OBJECTIVE
Asthma is a chronic airway disease characterized by airway remodeling, leading to a progressive decline in lung function. Therapeutic agents that attenuate airway remodeling can complement the limited effects of traditional glucocorticoids. In this study, we investigated the effect of resveratrol on allergic airway inflammation and remodeling in a murine model of chronic bronchial asthma.


METHODS
Peribronchial smooth muscle thickening that developed in mice challenged with a 3-month repeated exposure to ovalbumin (OVA) was used to study airway remodeling. Oral resveratrol was administered daily during the OVA challenge. The expression of TGF-β1/Smad signaling proteins and downstream mesenchymal markers in the presence or absence of resveratrol was examined in bronchial epithelial cells.


RESULTS
OVA sensitization and chronic challenge increased airway hyperresponsiveness, inflammation, goblet cell hyperplasia, α-smooth muscle actin (SMA), and collagen deposition. Resveratrol effectively suppressed OVA-induced airway inflammation and remodeling. The expression of TGF-β1/phosphorylated Smad2/3 was increased in the lung tissues of OVA-challenged mice but effectively inhibited by resveratrol. In bronchial epithelial cells, the TGF-β1-induced expression of the mesenchymal markers snail, slug, vimentin, and α-SMA was suppressed by resveratrol treatment.


CONCLUSIONS
Resveratrol effectively ameliorated both airway inflammation and airway structural changes in a mouse model of bronchial asthma. These effects were mediated by decreased TGF-β1 expression, in turn suppressing TGF-β1/Smad signaling and the epithelial-mesenchymal transition process. Our results demonstrate the potential benefits of resveratrol for the treatment of airway remodeling associated with bronchial asthma.
Division of Allergy, Pulmonary and Critical Care Medicine, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea.
Hwa Young
HY
Lee
Division of Allergy, Pulmonary and Critical Care Medicine, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea.
In Kyoung
IK
Kim
Division of Allergy, Pulmonary and Critical Care Medicine, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea.
Hyoung Kyu
HK
Yoon
Division of Allergy, Pulmonary and Critical Care Medicine, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea.
Soon Suk
SS
Kwon
Division of Allergy, Pulmonary and Critical Care Medicine, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea. chinkook@catholic.ac.kr.
Chin Kook
CK
Rhee
Division of Allergy, Pulmonary and Critical Care Medicine, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea. sooklee@catholic.ac.kr.
Sook Young
SY
Lee
Resveratrol; TGF-β1; airway remodeling