鼻息肉组织中BMP信号活性及E-cadherin表达失调与疾病进展的相关性研究
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摘要
目的：E-钙粘素(E-cadherin)为上皮细胞表面关键性粘附分子之一；本研究对比E-cadherin在慢性鼻鼻窦炎合并鼻息肉(chronic rhinosinusitis with nasal polyps, CRSwNP)及正常对照鼻粘膜组织中的表达差异,探讨E-cadherin与CRSwNP发病之间的联系。
方法：应用western blotting即免疫组化染色检测E-cadherin在CRSwNP和正常对照组织中的表达状态,比较其间的差异；依据Lund-Mackay CT评分系统评估CRSwNP患者之鼻窦CT。
结果：E-cadherin在CRSwNP组织中的表达较正常对照组明显上调(p=0.039),阳性染色主要见于上皮细胞膜,但CRSwNP组织中上皮细胞胞浆及核内亦见弱阳性着色；且CRSwNP组织中E-cadherin表达水平与其Lund-Mackay CT评分负相关(r=-0.604,p=0.005)。
结论：CRSwNP组织中E-cadherin的表达失调可能参与CRSwNP的发病并促进疾病的进展。
目的：骨形态蛋白(Bone morphogenetic proteins,BMPs)是一类多功能生长因子,其在组织维护和修复过程中发挥着重要作用；本研究对比BMP受体(ALK2,BMPR-IA, BMPR-IB and BMPRII)及BMP信号通路的核心介质pSmadl/5/8在伴和不伴鼻息肉的慢性鼻鼻窦炎(chronic rhinosinusitis with/without nasal polyps, CRSwNP/CRSsNP)以及正常鼻粘膜组织中的表达差异,探讨BMP信号活性与CRS发病之间的关系。
方法：应用蛋白质免疫印迹法及免疫组化染色检测BMP受体及pSmadl/5/8在CRSwNP、CRSsNP和正常对照组织中的表达状态；分别对CRSwNP患者之鼻窦CT、鼻内窥镜检查结果及症状进行评估。
结果：免疫组化染色显示pSmadl/5/8主要表达于上皮细胞核；而BMP受体阳性染色也主要见于上皮细胞膜,但同时部分炎性细胞也可明显表达BMP受体；除了ALK2的表达在CRSwNP及CRSsNP两组间无明显差异外,CRSwNP组织中pSmad1/5/8及BMP受体表达均较CRSsNP及对照组粘膜显著升高；而CRSsNP组织中仅ALK2及BMPR-IA两种受体表达明显高于正常对照组。CRSwNP组织中：pSmad1/5/8表达水平与BMP受体及E-cadherin表达均正相关；而pSmad1/5/8、ALK2、BMPR-IA及E-cadherin表达水平均与其相应的Lund-Mackay评分负相关。
结论：CRSwNP组织中BMP信号活性较CRSsNP及正常鼻粘膜明显升高,且其活性与CRSwNP的病情程度密切相关；BMP信号活性的失调可能在CRSwNP的发病机制中发挥着不可忽视的作用。
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-ⅠA, BMPR-ⅠB and BMPRⅡ) 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-ⅠA expression, whereas no significant difference in pSmad1/5/8, BMPR-ⅠB and BMPR-Ⅱexpression. 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.
方法：应用western blotting即免疫组化染色检测E-cadherin在CRSwNP和正常对照组织中的表达状态,比较其间的差异；依据Lund-Mackay CT评分系统评估CRSwNP患者之鼻窦CT。
结果：E-cadherin在CRSwNP组织中的表达较正常对照组明显上调(p=0.039),阳性染色主要见于上皮细胞膜,但CRSwNP组织中上皮细胞胞浆及核内亦见弱阳性着色；且CRSwNP组织中E-cadherin表达水平与其Lund-Mackay CT评分负相关(r=-0.604,p=0.005)。
结论：CRSwNP组织中E-cadherin的表达失调可能参与CRSwNP的发病并促进疾病的进展。
目的：骨形态蛋白(Bone morphogenetic proteins,BMPs)是一类多功能生长因子,其在组织维护和修复过程中发挥着重要作用；本研究对比BMP受体(ALK2,BMPR-IA, BMPR-IB and BMPRII)及BMP信号通路的核心介质pSmadl/5/8在伴和不伴鼻息肉的慢性鼻鼻窦炎(chronic rhinosinusitis with/without nasal polyps, CRSwNP/CRSsNP)以及正常鼻粘膜组织中的表达差异,探讨BMP信号活性与CRS发病之间的关系。
方法：应用蛋白质免疫印迹法及免疫组化染色检测BMP受体及pSmadl/5/8在CRSwNP、CRSsNP和正常对照组织中的表达状态；分别对CRSwNP患者之鼻窦CT、鼻内窥镜检查结果及症状进行评估。
结果：免疫组化染色显示pSmadl/5/8主要表达于上皮细胞核；而BMP受体阳性染色也主要见于上皮细胞膜,但同时部分炎性细胞也可明显表达BMP受体；除了ALK2的表达在CRSwNP及CRSsNP两组间无明显差异外,CRSwNP组织中pSmad1/5/8及BMP受体表达均较CRSsNP及对照组粘膜显著升高；而CRSsNP组织中仅ALK2及BMPR-IA两种受体表达明显高于正常对照组。CRSwNP组织中：pSmad1/5/8表达水平与BMP受体及E-cadherin表达均正相关；而pSmad1/5/8、ALK2、BMPR-IA及E-cadherin表达水平均与其相应的Lund-Mackay评分负相关。
结论：CRSwNP组织中BMP信号活性较CRSsNP及正常鼻粘膜明显升高,且其活性与CRSwNP的病情程度密切相关；BMP信号活性的失调可能在CRSwNP的发病机制中发挥着不可忽视的作用。
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-ⅠA, BMPR-ⅠB and BMPRⅡ) 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-ⅠA expression, whereas no significant difference in pSmad1/5/8, BMPR-ⅠB and BMPR-Ⅱexpression. 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.
引文
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1.耳鼻咽喉头颈外科学,孔维佳主编,人民卫生出版社。
2. Khalid AN, Quraishi SA, Kennedy DW. Long-term quality of life measures after functional endoscopic sinus surgery. Am J Rhinol 2004; 18:131-136
3. Pozehl D., Moeller P., Riechelmann H., et al:Distinct features of chronic rhinosinusitis with and without nasal polyps. Allergy 61.1275-1279.2006;
4. Meltzer E.O., Hamilos D.L., Hadley J.A., et al:Rhinosinusitis:establishing definitions for clinical research and patient care. Otolaryngol Head Neck Surg 131. (6 Suppl):S1-S62.2004;
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