Inhibitory Effects of Resveratrol on Airway Remodeling by Transforming Growth Factor-β/Smad Signaling Pathway in Chronic Asthma Model

Abstract

PurposeAsthma 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.MethodsPeribronchial 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.ResultsOVA 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.ConclusionsResveratrol 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.

ITGB4 deficiency induces senescence of airway epithelial cells through p53 activation

“…Cell senescence in the lung is closely related to the pathogenesis of asthma. The senescence of airway epithelial cells is associated with the development of asthma, such as airway remodeling . Thus, our results strongly suggest that senescence of airway epithelial cells after ITGB4 deficiency may have a close relationship to the pathogenesis of asthma.…”

Epithelial folliculin enhances airway inflammation in aspirin‐exacerbated respiratory disease

“…However, among the patients with AERD, highFLCN was not directly associated with the features of AERD such as severe asthma, airway hyperresponsiveness and CRS/NPs, indicating that serum FLCN may not be directly associated with key clinical features, but contribute to aggravating the severity of airway inflammation in AERD, as AERD subjects with highFLCN had a higher serum TGF‐β1 level. TGF‐β1 is produced from various cells, in which eosinophil‐derived TGF‐β1 is the major source for provoking the epithelial to mesenchymal transition, hence worsening airway inflammation and remodelling …”

“…TGF-β1 is produced from various cells, in which eosinophil-derived TGF-β1 is the major source for provoking the epithelial to mesenchymal transition, hence worsening airway inflammation and remodelling. 25,26 We targeted epithelial cells, an abundant source of FLCN in order to evaluate its role in AERD. 17 The The role of FLCN in maintaining the integrity of epithelial barrier has been extensively studied.…”

Resveratrol in Asthma: A French Paradox?

“…The natural sources of resveratrol are skin of grapes, several berries, and senna 5. In this issue, Lee et al6 reported the therapeutic effects of resveratrol in a murine model of allergic asthma. They showed that oral administration of resveratrol efficiently suppressed ovalbumin (OVA)-induced airway inflammation and remodeling.…”

“…Interestingly, in this issue Lee et al6 showed that resveratrol treatment suppressed epithelial-mesenchymal transition (EMT) markers, such as snail, slug, vimentin, and α-SMA. EMT is known to be induced by various environmental factors, and oxidative stress is one of the main triggers of EMT.…”