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Dysregulation Of BMP Signaling And E-cadherin In Chronic Rhinosinusitis With Nasal Polyps

Posted on:2011-07-30Degree:DoctorType:Dissertation
Country:ChinaCandidate:J H WuFull Text:PDF
GTID:1114360305492033Subject:Otorhinolaryngology
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Objectives:E-cadherin is a key epithelial protein and adhesive molecule, hence we compared E-cadherin expression between chronic rhinosinusitis patients with nasal polyps (CRSwNP) and controls, analyzed its possible role in the pathogenesis of CRSwNP.Methords:The expression of E-cadherin was compared between controls and CRSwNP by means of western blotting and immunohistochemistry. Computed tomography (CT) scan findings were scored by the Lund-Mackay CT scoring system.Results:There was up-regulation of E-cadherin in CRSwNP compared with controls (p= 0.039) and the positive staining was predominantly localized on the epithelial cell membrane. E-cadherin level correlated negatively with Lund-Mackay scores in CRSwNP(r =-0.604, p=0.005).Conclusion:E-cadherin may be involved in the pathogenesis of CRSwNP and correlates with disease severity. Objective:Bone morphogenetic proteins (BMPs) are multi-functional growth factors with important roles in the maintenance and repair of tissues; hence we compared the expression of the BMP pathway components between chronic rhinosinusitis (CRS) patients with and without nasal polyps (NP), analysed their association with disease severity, and explored the role of BMP signaling in the pathogenesis of CRSwNP.Methods:pSmad1/5/8 and BMP receptor (ALK2, BMPR-â… A, BMPR-â… B and BMPRâ…¡) levels were analyzed between controls and CRS patients with and without NP by means of western blotting and immunohistochemistry. Computed tomography (CT) and endoscopic appearances and symptoms were scored.Results:Immunohistochemical staining showed that pSmad1/5/8 expression was predominantly localized in epithelial cell nuclei. And BMP receptors were mainly expressed by epithelial cells, and some inflammatory-like cells also exhibited positive staining for such receptors. There were up-regulation of pSmad 1/5/8 and BMP receptors in CRSwNP in comparison with controls and CRSsNP, except for the insignificant difference in ALK2 expression between CRSwNP and CRSsNP. There was significant difference between controls and CRSsNP in ALK2 and BMPR-â… A expression, whereas no significant difference in pSmad1/5/8, BMPR-â… B and BMPR-â…¡expression. In CRSwNP, pSmad1/5/8 expression varied directly with BMP receptor levels. Furthermore, there was a positive correlation between pSmad 1/5/8 and E-cadherin expression in CRSwNP, and both of them inversely correlated with Lund-Mackay, endoscopic and symptom scores.Conclusions:BMP signaling is activated and correlates with disease severity in CRSwNP. The dysregulated BMP signaling may play an unnegligible role in pathologic mechanism of CRSwNP.
Keywords/Search Tags:E-cadherin, chronic rhinosinusitis, nasal polyps, Bone morphogenetic protein, BMP receptors, signaling
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