Browsing by Subject "MESENCHYMAL TRANSITION"

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    Anti-VEGF treatment suppresses remodeling factors and restores epithelial barrier function through the E-cadherin/β-catenin signaling axis in experimental asthma models
    (SPANDIDOS PUBL LTD) Türkeli, A; Yilmaz, Ö; Karaman, M; Kanik, ET; Firinci, F; Inan, S; Yüksel, H
    Besides maintaining a physical barrier with adherens junctional (AJ) and tight junctional proteins, airway epithelial cells have important roles in modulating the inflammatory processes of allergic asthma. E-cadherin and beta-catenin are the key AJ proteins that are involved in airway remodeling. Various mediators such as transforming growth factor-beta (TGF-beta), epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet derived growth factor (PDGF), insulin-like growth factor (IGF), tumor necrosis factor-alpha (TNF-alpha) and angiogenic factors, such as vascular endothelial growth factor (VEGF), are released by the airway epithelium in allergic asthma. The signaling pathways activated by these growth factors trigger epithelial-mesenchymal transition (EMT), which contributes to fibrosis and subsequent downregulation of E-cadherin. The present study used a mouse asthma model to investigate the effects of anti-VEGF, anti-TNF and corticosteroid therapies on growth factor and E-cadherin/beta-catenin expression. The study used 38 male BALB/c mice, divided into 5 groups. A chronic mouse asthma model was created by treating 4 of the groups with inhaled and intraperitoneal ovalbumin (n= 8 per group). Saline, anti-TNF-alpha (etanercept), anti-VEGF (bevacizumab) or a corticosteroid (dexamethasone) were applied to each group by intraperitoneal injection. No medication was administered to the control group (n=6). Immunohistochemistry for E-cadherin, beta-catenin and growth factors was performed on lung tissues and protein expression levels assessed using H-scores. Statistically significant differences were observed in E-cadherin, beta-catenin, EGF, FG, and PFGF (P<0.001 for all) as well as the IGF H-scores between the five groups (P<0.005). Only anti-VEGF treatment caused E-cadherin and beta-catenin levels to increase to the level of non-asthmatic control groups (P>0.005). All treatment groups had reduced TGF-beta, PDGF and FGF H-scores in comparison with the untreated asthma group (P=0.001). The EGF and IGF levels were not significantly different between the untreated asthmatic and non-asthmatic controls. The results suggested that anti-VEGF and TNF-alpha inhibition treatments are effective in decreasing growth factors, in a similar manner to conventional corticosteroid treatments. Anti-VEGF and TNF inhibition therapy may be an effective treatment for remodeling in asthma while offering an alternative therapeutic option to steroid protective agents. The data suggested that anti-VEGF treatment offered greater restoration of the epithelial barrier than both anti-TNF-alpha and corticosteroid treatment.
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    Airway epithelial barrier dysfunction in the pathogenesis and prognosis of respiratory tract diseases in childhood and adulthood
    (TAYLOR & FRANCIS AS) Yuksel, H; Turkeli, A
    The lungs are in direct contact with the environment through the tubular structure that constitutes the airway. Starting from the nasal orifice, the airway is exposed to foreign particles including infectious agents, allergens, and other substances that can damage the airways. Therefore, the airway must have a functional epithelial barrier both in the upper and lower airways to protect against these threats. As with the skin, it is likely that the pathogenesis of respiratory diseases is a consequence of epithelial barrier defects in these airways. The characteristics of this system, starting from the beginning of life and extending into maturing and aging, determine the prognosis of respiratory diseases. In this article, we discuss the pathogenesis, clinical phenotype, and prognosis of respiratory diseases from newborns to adulthood in the context of epithelial barrier function and dysfunction.
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    E-Cadherin: An Important Functional Molecule at Respiratory Barrier Between Defence and Dysfunction
    (FRONTIERS MEDIA SA) Yuksel, H; Ocalan, M; Yilmaz, O
    While breathing, many microorganisms, harmful environmental particles, allergens, and environmental pollutants enter the human airways. The human respiratory tract is lined with epithelial cells that act as a functional barrier to these harmful factors and provide homeostasis between external and internal environment. Intercellular epithelial junctional proteins play a role in the formation of the barrier. E-cadherin is a calcium-dependent adhesion molecule and one of the most important molecules involved in intercellular epithelial barier formation. E-cadherin is not only physical barrier element but also regulates cell proliferation, differentiation and the immune response to environmental noxious agents through various transcription factors. In this study, we aimed to review the role of E-cadherin in the formation of airway epithelial barier, its status as a result of exposure to various environmental triggers, and respiratory diseases associated with its dysfunction. Moreover, the situations in which its abnormal activation can be noxious would be discussed.