Reduced Proliferative Capacity and Defense against <i>Staphylococcus aureus</i> in Human Nasal Mucosal Epithelium Lacking ZNF365

<b><i>Introduction:</i></b> Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic inflammatory disease of the nose characterized by barrier disruption and environmental susceptibility, and the deletion of ZNF365 may be a factor inducing these manifestations. However, there is no study on the mechanism of action between CRSwNP and ZNF365. Therefore, this study focuses on the effect of the zinc finger protein ZNF365 on the proliferation of nasal mucosal epithelial cells and their defense against <i>Staphylococcus aureus</i> (<i>S. aureus</i>). <b><i>Methods:</i></b> Immunohistochemistry and Western blot were applied to verify the changes of ZNF365 expression in nasal polyp tissues and control tissues, as well as in primary epithelial cells. ZNF365 was knocked down in human nasal mucosa epithelial cell line (HNEpc), and the proliferation, migration, and transdifferentiation of epithelium were observed by immunofluorescence, QPCR, CCK8, and cell scratch assay. The changes of mesenchymal markers and TLR4-MAPK-NF-κB pathway were also observed after the addition of <i>S. aureus</i>. <b><i>Results:</i></b> ZNF365 expression was reduced in NP tissues and primary nasal mucosal epithelial cells compared to controls. Knockdown of ZNF365 in HNEpc resulted in decreased proliferation and migration ability of epithelial cells and abnormal epithelial differentiation (decreased expression of tight junction proteins). <i>S. aureus</i> stimulation further inhibited epithelial cell proliferation and migration, while elevated markers of epithelial-mesenchymal transition and inflammatory responses occurred. <b><i>Conclusion:</i></b> ZNF365 is instrumental in maintaining the proliferative capacity of nasal mucosal epithelial cells and defending against the invasion of <i>S. aureus</i>. The findings suggest that ZNF365 may participate in the development of CRSwNP.