Abstract:OBJECTIVE: To investigate the roles of FIZZ1 and NOTCH1 in the pathogenesis of asthma and the effect of rosiglitazone on airway remodeling. METHODS: Forty-five healthy 6 to 8-week-old Sprague-Dawley rats were randomly divided into a control group and asthma groups with and without rosiglitazone treatment. The paraffin slices of lung tissues were made to assess the histological changes. a-SMA protein, a specific marker of airway remodeling, in lung tissues was measured by immunohistochemistry. FIZZl-mRNA and NOTCH1-mRNA expression in lung tissues was measured by RT-PCR. RESULTS: The characteristic changes of airway remodeling were observed in the untreated asthma group. The histological changes in the airway were less severe in the rosiglitazone treated asthma group. Positive a-SMA staining, FIZZl-mRNA and NOTCH1-mRNA were highly expressed in peribronchial lung sections isolated from the untreated asthma group. Rosiglitazone treatment decreased significantly the expression of a-SMA protein, FIZZl-mRNA and NOTCH1-mRNA compared with the untreated asthma group, but the expression of a-SMA protein, FIZZl-mRNA and NOTCH1-mRNA in the rosiglitazone treated asthma group remained higher than the control group. a-SMA expression was positively correlated with FIZZl-mRNA (r=0.826, P＜0.01) and NOTCH1-mRNA expression (r=0.9, P<0.01). FIZZl-mRNA expression was positively correlated with NOTCH1-mRNA expression (r=0.76, P<0.01). CONCLUSIONS: FIZZl and NOTCH1 may induce an increase in a-SMA expression. FIZZl and NOTCH1 play a critical role in the process of airway remodeling. Rosiglitazone treatment may inhibit airway remodeling in asthmatic rats.
