The expression of WNT signaling in chronic murine asthma model and asthmatic patients

Abstract

Background: Airway remodeling is a harmful consequence of the impaired lung function in asthmatic patients, but the factors associated with it are not known. WNT signaling pathway might be suggested as a critical determinant of airway remodeling in asthmatic patients but there were few reports about direct association between asthma and WNT signal. The author used a murine chronic asthma model to investigate the possible role of WNT signaling in remodeling. Methods: BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injections on days 0 and 7 (sensitization), and some of the mice then received intranasal OVA twice a week between day 14 and day 94 (challenges). The OVA-treated mice were examined by the methacholine provocation test and bronchoalveolar lavage. Samples of murine lung tissue were obtained for histology and quantitative real-time PCR of WNT family and β-catenin genes. In addition, sputum samples were obtained from asthmatic patients by the induced sputum procedure and analyzed by quantitative real-time PCR. Results: The methacholine test revealed increases in maximal inducible bronchoconstriction in the both asthmatic groups. There were extensive eosinophil and mononuclear cell inflammatory responses, goblet cell hyperplasia, and mucus hypersecretion of the airways in both the acute and chronic murine asthma groups. Real-time PCR revealed that β-catenin, WNT5a, and WNT7a were up-regulated in the chronic asthma group, and immunohistochemistry revealed greatly elevated expression of β-catenin in the lung tissues of the mice in this group. Real-time PCR of sputum samples from chronic human asthma patients revealed higher levels of WNT7a than in the control group and these were correlated with the FEV1/FVC ratio. Conclusion: WNT/β-catenin signaling appears to contribute to airway remodeling in chronic asthma, and pathway of WNT7a may be a key role in this process.