Anti-VEGF treatment suppresses remodeling factors and restores epithelial barrier function through the E-cadherin/β-catenin signaling axis in experimental asthma models

Simple item page
dc.contributor.authorTürkeli, A
dc.contributor.authorYilmaz, Ö
dc.contributor.authorKaraman, M
dc.contributor.authorKanik, ET
dc.contributor.authorFirinci, F
dc.contributor.authorInan, S
dc.contributor.authorYüksel, H
dc.date.accessioned2024-07-18T12:03:20Z
dc.date.available2024-07-18T12:03:20Z
dc.description.abstractBesides 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.
dc.identifier.issn1792-0981
dc.identifier.other1792-1015
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/9062
dc.language.isoEnglish
dc.publisherSPANDIDOS PUBL LTD
dc.subjectENDOTHELIAL GROWTH-FACTOR
dc.subjectTNF-ALPHA
dc.subjectMESENCHYMAL TRANSITION
dc.subjectAIRWAY INFLAMMATION
dc.subjectTIGHT JUNCTIONS
dc.subjectEXPRESSION
dc.subjectCELLS
dc.subjectINHIBITORS
dc.subjectDEXAMETHASONE
dc.subjectDYSFUNCTION
dc.titleAnti-VEGF treatment suppresses remodeling factors and restores epithelial barrier function through the E-cadherin/β-catenin signaling axis in experimental asthma models
dc.typeArticle

Files

Collections

Web of Science Koleksiyonu