Expression and Regulation of Transcription Factor FoxA2 in Chronic Rhinosinusitis With and Without Nasal Polyps

Purpose: Chronic rhinosinusitis (CRS) is characterized by the excessive production of mucus. However, the molecular mechanism underlying mucin overproduction in CRS with or without nasal polyps (CRSwNP and CRSsNP, respectively) is poorly understood. This study was conducted to assess the importance of the transcription factor FoxA2 in mucin production and to investigate the targeting of FoxA2 as a potential therapeutic strategy for mucus hypersecretion in CRS patients.

Methods: We enrolled 15 CRSwNP patients, 15 CRSsNP patients, and 10 normal controls in this study. The expression levels of FoxA2, MUC5AC, and MUC5B in inflamed and healthy nasal tissues were examined via immunohistochemistry and quantitative reverse transcription-polymerase chain reaction, and the levels of several proinflammatory cytokines in nasal secretions were measured via FlowCytomix analysis. In addition, the expression of MUC5AC and FoxA2 was determined in polyp-derived epithelial cells and NCI-H292 cells after in vitro stimulation.

Results: FoxA2 was significantly down-regulated, and MUC5AC and MUC5B were significantly up-regulated in both the CRSwNP and CRSsNP patients compared to the controls (P<0.05), and the protein level of FoxA2 was negatively associated with the IL-6 level in the CRS patients (P<0.05). IL-6 significantly increased MUC5AC expression but inhibited FoxA2 expression in vitro (P<0.05). Transfection with a FoxA2 expression plasmid significantly decreased MUC5AC promoter activity (P<0.05) and inhibited IL-6-induced MUC5AC production (P<0.05). In addition, clarithromycin significantly alleviated IL-6-induced FoxA2 suppression and decreased MUC5AC expression in vitro (P<0.05).

Conclusions: Our findings suggest that FoxA2 may be considered a therapeutic target for the modulation of mucus hypersecretion in CRS patients.