IL‐13 May Could Enhance the Proliferation and Affect the Differentiation of Nasal Epithelium Basal Cells Through the mTOR/p70S6K1 Pathway in Chronic Rhinosinusitis With Nasal Polyps

Background: One of the hallmarks of Chronic rhinosinusitis with nasal polyps (CRSwNP) is the overexpression of IL‐13, which may influence the proliferation and differentiation of nasal epithelial basal cells. However, the pathway is not clear enough, and the mTOR/p70S6K1 pathway is related to cell growth. This study was trying to explore if IL‐13 could impact nasal epithelial basal cells through the mTOR/p70S6K1 pathway. Methods: PCR, western blot (WB), and immunohistochemistry (IHC) were used to compare the difference between IL‐13 and the mTOR/p70S6K1 pathway‐related molecules expression level between the healthy control (HC) and CRSwNP groups. WB, 5‐ethynyl‐2 ′ ‐deoxyuridine staining, and Immunofluorescent (IF) were performed on human nasal epithelial progenitor cells (HNEPCs) to detect the proliferation ability under the effect of IL‐13. In addition, qRT‐PCR, WB, and IF were used to detect the differentiation ability with the stimulation of IL‐13 in the air‐liquid interface (ALI) system. Results: The expression of IL‐13, mTOR/p70S6K1‐related molecules, and proliferation‐related molecules Ki67, CDK2, and cyclin E1 were upregulated in CRSwNP compared to HC. In HNEPCs, IL‐13 could stimulate nasal epithelial cells proliferating through the mTOR/p70S6K1 pathway, and this phenomenon could be inhibited when mTOR (with rapamycin) and S6K1 (with PF‐4708671) were blocked. In the ALI system, the effect of IL‐13 added in the proliferation phase could persist in the proliferation and differentiation stage, affecting the nasal epithelial progenitor/stem cells’ irregular differentiation. Conclusion: IL‐13 may affect the proliferation and differentiation of nasal epithelial progenitor/stem cells through the mTOR/p70S6K1 pathway, which may affect the development of nasal polyps.