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