The diverse roles of YAP in the regulation of human nasal epithelial remodeling

Abstract

Yes-associated protein (YAP) is essential in maintaining tissue size. Aberrant epithelial remodeling is a key pathological alteration in both inflammation and benign tumors in nasal mucosa. We sought to investigate the expression and localization patterns of YAP in remodeled nasal epithelium of basal cell hyperplasia, goblet cell metaplasia and squamous metaplasia. YAP expression patterns were evaluated in tissues obtained from patients with NP (n = 45) and IP (n = 27), and control subjects with septal deviation (n = 17) and tissue-derived primary cell cultures. Compared to the normal epithelium, expressions of YAP were significantly higher in basal cell hyperplasia (NP, 11.4-fold; IP, 19.6-fold), followed by squamous metaplasia (8.2-fold) and mild to moderate goblet cell metaplasia (2.9-fold); while their expression was lower in severe goblet cell metaplasia (3.3-fold). Our resultsshowed that: 1) ectopic nuclear YAP expression associated with p63+ basal cell hyperplasia and the high proliferative potential epithelial cells; 2) increase of cytoplasmic YAP correlated with mild to moderate goblet cell metaplasia; 3) increase of cytoplasmic YAP correlated with squamous cell metaplasia. The in vitro cell model also demonstrated almost concordant changes of YAP with the mucosa findings. Different YAP expression and localization patterns should play critical but differential roles in the nasal epithelial remodeling processes under mucosal inflammation and benign tumor formation.

Keywords: Epithelial remodeling; Hippo pathway; Nasal benign tumor; Nasal mucosal inflammation; YAP.