Smad信号通路在慢性鼻-鼻窦炎伴鼻息肉和不伴鼻息肉的黏膜上皮修复机制中的作用

The role of Smad signaling pathway in the repair of mucosal epithelium in chronic sinusitis with nasal polyps and without nasal polyps

目的:探讨TGF-β-Smad信号通路在慢性鼻-鼻窦炎(CRS)不伴鼻息肉(CRSsNP)和伴鼻息肉(CRSwNP)的黏膜上皮细胞修复中的作用。方法:通过蛋白免疫印迹检测CRS患者与正常对照组的筛窦黏膜上皮标本中TGF-β1、TGF-βRⅠ、TGF-βRⅡ、Smad3、pSmad3、Smad7和Smad锚受体的表达。在TGF-β1和(或)抑制剂刺激后,运用MTT法检测黏膜上皮细胞的增殖水平。结果:与正常对照组相比,在CRSsNP中TGF-β1、TGF-βRⅠ和Smad3蛋白表达水平显著增高,而CRSwNP中TGF-β1和Smad3的表达则明显降低。另外,pSmad3在CRS 2种分型中的表达均降低;Smad7蛋白均显著高于正常对照组。MTT结果显示,正常对照组和CRS组TGF-β1均抑制了EGF诱导黏膜上皮细胞的增殖,该抑制作用可以被TGF-β1受体抑制剂(SB431542)所阻断。结论:与正常对照组相比,CRSwNP黏膜上皮表现为TGF-β信号通路低表达的特点;CRSsNP黏膜上皮TGF-β1信号高表达。Smad7蛋白的高表达可能导致了下游信号pSmad3的低表达,进而影响了TGF-β对上皮细胞增殖的抑制作用,但CRSsNP与CRSwNP黏膜上皮细胞增殖水平并未表现出显著差异。

Objective:To evaluate the differences in CRS and normal subjects between chronic rhinosinusitis without nasal polys(CRSsNP)and chronic rhinosinusitis with nasal polys(CRSwNP)in the role of TGF-β-Smad pathways in the repair of mucosal epithelium.Method:Ethmoidal mucosal samples collected from CRS and healthy control patients were analyzed for TGF-β1,TGF-βreceptor Ⅰ,TGF-βreceptor Ⅱ,Smad3,phospho-Smad3,Smad7,and Smad anchor for receptor activation by Western blot.The proliferation of sinonasal epithelial cells at baseline after TGF-β1 and/or EGF stimulation was evaluated by the MTT assay.Result:In CRSsNP,TGF-β1,TGF-βreceptorⅠ,TGF-βreceptorⅡand Smad3 protein levels were significantly higher than controls.In CRSwNP,TGF-β1,Smad3 and pSmad3 protein levels were significantly lower than controls.Smad7 protein was significantly higher in CRS than controls.In vitro experiments demonstrated that the baseline proliferation levels of sinonasal epithelial cells were lower in CRS than controls.Conclusion:CRSwNP is characterized by a lower level of TGF-signaling compared with the control.In CRSsNP,although the upstream signaling of TGF-βwas enhanced,over expression of Smad7 protein may restrain the downstream signaling components(e.g.,pSmad3)and the TGF-βantiproliferative effect on sinonasal epithelium.The difference in the local tissue concentration of TGF-β1 between CRSsNP and CRSwNP patients did not show significant differences in epithelial proliferation.