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The following is a summary of “Hypoxia-reduced YAP phosphorylation enhances expression of Mucin5AC in nasal epithelial cells of chronic rhinosinusitis with nasal polyps,” published in the November 2024 issue of Allergy and Immunology by Zhong et al.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory upper respiratory disease. The mechanism behind abnormal Mucin5AC expression in CRSwNP epithelial cells remains unclear.
Researchers conducted a retrospective study to investigate the role of yes-associated protein (YAP) in the mechanism of excessive Mucin5AC expression in CRSwNP.
They analyzed tissue biopsies from CRSwNP (n = 60), CRSsNP (n = 9), and healthy controls (n = 30). They also used a hypoxic model of primary human nasal epithelial cells (hNECs) to assess the expression levels of HIF-1α and YAP and evaluated the effect of the signaling axis on mucus secretion in hNECs.
The results showed elevated YAP expression in CRSwNP and CRSsNP compared to controls, with higher HIF-1α levels in CRSwNP. Under hypoxia, HIF-1α upregulated YAP by reducing its phosphorylation, inhibiting LATS 1, and preventing YAP degradation. HIF-1α also promoted P63 expression and increased Mucin5AC levels in hNECs through enhanced YAP activation.
They found that hypoxia enhanced YAP activation by reducing p-LATS 1 and YAP phosphorylation. This likely contributed to basal cell proliferation, goblet cell differentiation, and excessive Mucin5AC expression in CRSwNP.
Source: onlinelibrary.wiley.com/doi/10.1111/all.16394
