FIZZ1诱导气道上皮间质转化导致哮喘早期气道重塑

山东大学学报(医学版) ›› 2010, Vol. 48 ›› Issue (2): 80-84.

FIZZ1诱导气道上皮间质转化导致哮喘早期气道重塑

姬峰，李艳丽，郝俊清，李鸿佳，董亮

山东大学齐鲁医院呼吸科，济南 250012

收稿日期:2009-05-13 出版日期:2010-02-16 发布日期:2010-02-16
通讯作者: 董亮(1964- )，男，教授，主要从事支气管哮喘气道重塑的研究
作者简介:姬峰(1979- )，男，主治医师，硕士研究生，主要从事支气管哮喘气道重塑的研究。 E-mail：jifeng8164@sina.com

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

JI Feng， LI Yanli, HAO Junqing, LI Hongjia， DONG Liang

Department of Pulmonary Diseases， Qilu Hospital of Shandong University， Jinan 250012， China

Received:2009-05-13 Online:2010-02-16 Published:2010-02-16

摘要/Abstract

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。

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

Abstract:

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 mouse epithelial cells with FIZZ1 recombination protein and FIZZ1-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 Fibronectin1, 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-Cadherin expression; while FIZZ1-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.

Key words: Asthma； Mice， inbred BALB C； Airway remodeling; FIZZ1； Epithelial mesenchymal transition

中图分类号:

R562.2+5

姬峰，李艳丽，郝俊清，李鸿佳，董亮. FIZZ1诱导气道上皮间质转化导致哮喘早期气道重塑[J]. 山东大学学报(医学版), 2010, 48(2): 80-84.

JI Feng， LI Yanli, HAO Junqing, LI Hongjia， DONG Liang. FIZZ1 induces airway epithelial to mesenchymal transition leading to early airway remodeling in asthma[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(2): 80-84.

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