FIZZ1诱导气道上皮间质转化导致哮喘早期气道重塑

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.

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

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 FIZZ1,type I collagen,Fibronectin 1 and E-Cadherin in the lungs were determined by quantitative real-time PCR.After treatment of cultured mous...