E-cadherin: gatekeeper of airway mucosa and allergic sensitization

Nawijn, Martijn C.; Hackett, Tillie L.; Postma, Dirkje S.; Oosterhout, Antoon J. M. van; Heijink, Irene H.

doi:10.1016/j.it.2011.03.004

Cited by 189 publications

(212 citation statements)

References 90 publications

(119 reference statements)

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“…In asthma, the mucosal barrier function can be damaged due to disrupted expression of E-cadherin. 33 Accordingly, kaempferol may be effective in preserving the barrier function of airway epithelium by enhancing E-cadherin level.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of airway epithelial-to-mesenchymal transition and fibrosis by kaempferol in endotoxin-induced epithelial cells and ovalbumin-sensitized mice

Gong

Cho

Shin

et al. 2014

Laboratory Investigation

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Chronic airway remodeling is characterized by structural changes within the airway wall, including smooth muscle hypertrophy, submucosal fibrosis and epithelial shedding. Epithelial-to-mesenchymal transition (EMT) is a fundamental mechanism of organ fibrosis, which can be induced by TGF-b. In the in vitro study, we investigated whether 1-20 mM kaempferol inhibited lipopolysaccharide (LPS)-induced bronchial EMT in BEAS-2B cells. The in vivo study explored demoting effects of 10-20 mg/kg kaempferol on airway fibrosis in BALB/c mice sensitized with ovalbumin (OVA). LPS induced airway epithelial TGF-b1 signaling that promoted EMT with concurrent loss of E-cadherin and induction of a-smooth muscle actin (a-SMA). Nontoxic kaempferol significantly inhibited TGF-b-induced EMT process through reversing E-cadherin expression and retarding the induction of N-cadherin and a-SMA. Consistently, OVA inhalation resulted in a striking loss of epithelial morphology by displaying myofibroblast appearance, which led to bronchial fibrosis with submucosal accumulation of collagen fibers. Oral administration of kaempferol suppressed collagen deposition, epithelial excrescency and goblet hyperplasia observed in the lung of OVA-challenged mice. The specific inhibition of TGF-b entailed epithelial protease-activated receptor-1 (PAR-1) as with 20 mM kaempferol. The epithelial PAR-1 inhibition by SCH-79797 restored E-cadherin induction and deterred a-SMA induction, indicating that epithelial PAR-1 localization was responsible for resulting in airway EMT. These results demonstrate that dietary kaempferol alleviated fibrotic airway remodeling via bronchial EMT by modulating PAR1 activation. Therefore, kaempferol may be a potential therapeutic agent targeting asthmatic airway constriction.

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Section: Discussionmentioning

confidence: 99%

Inhibition of airway epithelial-to-mesenchymal transition and fibrosis by kaempferol in endotoxin-induced epithelial cells and ovalbumin-sensitized mice

Gong

Cho

Shin

et al. 2014

Laboratory Investigation

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“…72 Exposure and stress of the epithelium leads to the production of different cytokines, which induce certain immune responses, and can also be involved in aberrant or uncontrolled tissue repair. 73,74 Remodeling processes in the airways include hypertrophy and migration of ASM, goblet cell metaplasia, basal membrane thickening, subepithelial fibrosis, and airway neovascularization.…”

Section: Role Of Wnt Pathways In Airway Remodelingmentioning

confidence: 99%

Take the Wnt out of the inflammatory sails: modulatory effects of Wnt in airway diseases

Reuter

Beckert

Taube

2016

Laboratory Investigation

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Bronchial asthma and chronic obstructive pulmonary disease (COPD) are chronic diseases that are associated with inflammation and structural changes in the airways and lungs. Recent findings have implicated Wnt pathways in critically regulating inflammatory responses, especially in asthma. Furthermore, canonical and noncanonical Wnt pathways are involved in structural changes such as airway remodeling, goblet cell metaplasia, and airway smooth muscle (ASM) proliferation. In COPD, Wnt pathways are not only associated with structural changes in the airways but also involved in the development of emphysema. The present review summarizes the role and function of the canonical and noncanonical Wnt pathway with regard to airway inflammation and structural changes in asthma and COPD. Further identification of the role and function of different Wnt molecules and pathways could help to develop novel therapeutic options for these diseases.

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“…After chronic aggression, the epithelium is able to modulate the innate immune response and adaptive immune response by interacting with cells from the immune system, but also by secreting soluble factors such as TGF-b, epidermal growth factor, FGF2, IGF1, PDGF and endothelin-1 [126,127]. All these modifications contribute to the proliferation and differentiation of fibroblasts and myofibroblasts, and to the accumulation of fibronectin and collagen in the lamina reticularis leading to the thickening of the bronchial wall.…”

Section: Emt In Chronic Bronchial Diseases Emt and Allergic Asthmamentioning

confidence: 99%

Tissue remodelling in chronic bronchial diseases: from the epithelial to mesenchymal phenotype

et al. 2014

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Airway remodelling is a critical feature of chronic bronchial diseases, characterised by aberrant repair of the epithelium and accumulation of fibroblasts, which contribute to extracellular matrix (ECM) deposition resulting in fixed bronchial obstruction. Recently, epithelial-mesenchymal transition (EMT) has been identified as a new source of fibroblasts that could contribute to the remodelling of the airways. This phenomenon consists of the loss of the epithelial phenotype by bronchial epithelial cells and the acquisition of a mesenchymal phenotype. These cells are then able to migrate and secrete ECM molecules. Herein, we review the different types of EMT. We will then focus on the signalling pathways that are involved, such as transforming growth factor-b and Wnt, as well as the more recently described Sonic Hedgehog pathway. Finally, we will highlight the implication of EMT in airway remodelling in specific chronic bronchial pathologies, such as asthma, chronic obstructive pulmonary disease and bronchiolitis obliterans following lung transplantation. Despite the limitations of in vitro models, future studies of EMT in vivo are warranted to shed new light on the pathomechanisms of bronchial obstruction. @ERSpublications Epithelial-mesenchymal transition in chronic bronchial remodelling diseases

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E-cadherin: gatekeeper of airway mucosa and allergic sensitization

Cited by 189 publications

References 90 publications

Inhibition of airway epithelial-to-mesenchymal transition and fibrosis by kaempferol in endotoxin-induced epithelial cells and ovalbumin-sensitized mice

Inhibition of airway epithelial-to-mesenchymal transition and fibrosis by kaempferol in endotoxin-induced epithelial cells and ovalbumin-sensitized mice

Take the Wnt out of the inflammatory sails: modulatory effects of Wnt in airway diseases

Tissue remodelling in chronic bronchial diseases: from the epithelial to mesenchymal phenotype

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