FIZZ1诱导气道上皮间质转化导致哮喘早期气道重塑  

FIZZ1 induces airway epithelial to mesenchymal transition leading to early airway remodeling in asthma

作　　者：姬峰[1] 李艳丽[1] 郝俊清[1] 李鸿佳[1] 董亮[1] 

机构地区：[1]山东大学齐鲁医院呼吸科,济南250012

出　　处：《山东大学学报（医学版）》2010年第2期80-84,共5页Journal of Shandong University:Health Sciences

摘　　要：目的观察FIZZ1在小鼠哮喘模型气道上皮间质转化(EMT)中的作用,探讨FIZZ1引起哮喘早期气道重塑的机制。方法随机将BALB/c小鼠分为哮喘模型组(OVA组)和正常对照组。采用免疫组织化学法测定小鼠气道上皮中FIZZ1蛋白的表达,采用实时定量-聚合酶链反应法检测小鼠肺组织中FIZZ1mRNA、Ⅰ型胶原、纤维连接蛋白1、E钙粘蛋白的表达,采用小鼠肺上皮细胞(MLE-12)体外原代培养,FIZZ1重组蛋白及FIZZ1-shRNA干预,免疫印迹法检测E钙粘蛋白、Ⅰ型胶原和纤维连接蛋白1的表达。结果与对照组相比,OVA组小鼠气道上皮中FIZZ1、FIZZ1mRNA表达显著增强,Ⅰ型胶原和纤维连接蛋白1显著增高,E钙粘蛋白明显降低,并且分别与FIZZ1呈正相关和负相关;体外原代培养MLE-12,FIZZ1重组蛋白干预,Ⅰ型胶原和纤维连接蛋白1增高,E钙粘蛋白显著降低;FIZZ1-shRNA干预,蛋白表达正常。结论FIZZ1作为EMT的一个潜在诱导剂,诱导E钙粘蛋白表达减少,而Ⅰ型胶原和纤维连接蛋白1表达增加,从而诱导哮喘早期气道重塑。Objective To explore the effect of FIZZ1 on epithelial to mesenchymal transition （EMT） in a murine asthma model, and to investigate the mechanisms of FIZZ1 leading to early airway remodeling. Methods BALB/c mice were randomly divided into 2 groups： the OVA group and the control group. FIZZ1 levels in airway epithelium were determined by immunohistochemistry. Expressions of F/ZZ1, type I collagen, Fibronectin 1 and E-Cadherin in the lungs were determined by quantitative real-time PCR. After treatment of cultured mouse epithelial ceils with FIZZ1 recombination protein and FIZZI-shRNA, expressions of type I collagen, Fibronectin 1 and E-Cadherin were determined by Western blot. Results Expressions of FIZZ1, FIZZ1 mRNA, type I collagen and Fibronectin 1 in the OVA group were significantly increased compared with those in the control group, while E-Cadherin obviously decreased. Expression of FIZZ1 had positive correlations with expressions of type I collagen and Fibronectinl, and a negative correlation with that of E-Cadherin. In cultured mouse epithelial cells, FIZZ1 recombination protein up-regulated expressions of type I collagen and Fibronectin 1, and down-regulated E-Cadheriu expression ; while FIZZI-shRNA had no effect on expressions of type I collagen, Fibronectin 1 and E-Cadherin. Conclusion FIZZ1 is a potent inducer of epithelial to mesenchymal transition. It down-regulates E-Cadherin expression but up-regulates expressions of type I collagen and Fibronectin 1, by which FIZZ1 could play a role in early airway remodeling in asthma.

关 键 词：哮喘 小鼠 近交BALB C 气道重塑 炎症因子 上皮间质转化 

分 类 号：R562.25[医药卫生—呼吸系统]