Upregulation of Basonuclin1 Is Associated with p63-Involved Epithelial Barrier Impairment and Type-2 Helper T-cell Inflammation in Chronic Rhinosinusitis with Nasal Polyps

Abstract

<b><i>Background:</i></b> Tumor protein p63 has been shown to be important for epithelial dysfunction, including epithelial barrier defects and mucosal inflammation, in the development of chronic rhinosinusitis with nasal polyps (CRSwNP). Basonuclin1 (BNC1), an epithelial-specific transcriptional factor, is a direct downstream target of p63 and thus might be involved in the pathogenesis of CRSwNP. <b><i>Objective:</i></b> We sought to investigate whether BNC1 was associated with p63-mediated epithelial barrier defects and nasal mucosal inflammation in CRSwNP. <b><i>Methods:</i></b> Nasal tissue biopsies were obtained from 91 patients to CRSwNP, 49 chronic rhinosinusitis without nasal polyps (CRSsNP) patients, and 28 control subjects. Immunohistochemistry and immunofluorescence staining were used to determine the distribution of BNC1 in tissues and localization in cells, respectively. Quantitative PCR was performed to detect the expression levels of <i>BNC1</i>, <i>TP63</i>, epithelial barrier proteins, and type-2 helper T-cell inflammation-related genes. <b><i>Results:</i></b> <i>BNC1</i> mRNA expression was significantly elevated in the tissues in CRSwNP patients compared with CRSsNP (1.96-fold, <i>p</i> = 0.0003) and control groups (2.40-fold, <i>p</i> < 0.0001). <i>BNC1</i> staining was strongly positive in the nasal epithelium and co-localized with p63-positive epithelial cells. The expression of <i>BNC1</i> mRNA was strongly correlated with <i>TP63</i> mRNA level both in tissue biopsies (<i>r</i> = 0.78, <i>p</i> < 0.0001) and epithelial scrapings (<i>r</i> = 0.97, <i>p</i> < 0.0001). <i>BNC1</i> expression was also positively correlated with epithelial barrier protein genes (<i>CDH1</i>, <i>CLDN1</i>, <i>CLDN4</i>, <i>TJP1,</i> and <i>TJP2</i>) and epithelial genes involved in T<sub>H</sub>2 inflammation (<i>IL33</i>, <i>CCL26</i>, <i>CLC</i>, and <i>ALOX15</i>). <b><i>Conclusions:</i></b> Overexpression of <i>BNC1</i> may be associated with increased expression of <i>TP63</i>, and possibly contribute to the epithelial barrier defects and T<sub>H</sub>2 inflammation in CRSwNP.

Epithelial Barrier in the Nasal Mucosa, Related Risk Factors and Diseases

“…Pathological evidence shows that CRS with nasal polyps (CRSwNPs) represents Th2 reaction and eosinophil (EOS) infiltration [22,23]. The same epithelial barrier dysfunction has also been observed in CRS [24].…”