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

BACKGROUND:

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.

OBJECTIVE:

We sought to investigate whether BNC1 was associated with p63-mediated epithelial barrier defects and nasal mucosal inflammation in CRSwNP.

METHODS:

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 BNC1, TP63, epithelial barrier proteins, and type-2 helper T-cell inflammation-related genes.

RESULTS:

BNC1 mRNA expression was significantly elevated in the tissues in CRSwNP patients compared with CRSsNP (1.96-fold, p = 0.0003) and control groups (2.40-fold, p < 0.0001). BNC1 staining was strongly positive in the nasal epithelium and co-localized with p63-positive epithelial cells. The expression of BNC1 mRNA was strongly correlated with TP63 mRNA level both in tissue biopsies (r = 0.78, p < 0.0001) and epithelial scrapings (r = 0.97, p < 0.0001). BNC1 expression was also positively correlated with epithelial barrier protein genes (CDH1, CLDN1, CLDN4, TJP1, and TJP2) and epithelial genes involved in TH2 inflammation (IL33, CCL26, CLC, and ALOX15).

CONCLUSIONS:

Overexpression of BNC1 may be associated with increased expression of TP63, and possibly contribute to the epithelial barrier defects and TH2 inflammation in CRSwNP.

• Authors: Yunbo Gao, Jingyun Li, Jian Jiao, Ying Li, Chengshuo Wang, Yuan Zhang, Luo Zhang
• Journal: International archives of allergy and immunology (Int Arch Allergy Immunol) 2021 Vol. 182 Issue 11 Pg. 1046-1057 ISSN: 1423-0097 [Electronic] Switzerland
• PMID: 34148047 (Publication Type: Journal Article)
• Copyright: © 2021 S. Karger AG, Basel.

Chemical References

• DNA-Binding Proteins
• TP63 protein, human
• Tight Junction Proteins
• Transcription Factors
• Tumor Suppressor Proteins
• BNC1 protein, human

Topics

• Adult
• Chronic Disease
• DNA-Binding Proteins (genetics, immunology)
• Female
• Humans
• Male
• Middle Aged
• Nasal Mucosa (immunology)
• Nasal Polyps (immunology)
• Rhinitis (immunology)
• Sinusitis (immunology)
• Th2 Cells (immunology)
• Tight Junction Proteins (genetics, immunology)
• Tight Junctions (immunology)
• Transcription Factors (genetics, immunology)
• Tumor Suppressor Proteins (genetics, immunology)
• Up-Regulation