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 #x3c; 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 #x3c; 0.0001) and epithelial scrapings (r = 0.97, p #x3c; 0.0001). BNC1 expression was also positively correlated with epithelial barrier protein genes (CDH1, CLDN1, CLDN4, TJP1, and TJP2) and epithelial genes involved in T_H2 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 T_H2 inflammation in CRSwNP.
Int Arch Allergy Immunol

中文翻译：

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Basonuclin1的上调与慢性鼻息肉鼻窦炎中p63参与的上皮屏障受损和2型辅助T细胞炎症有关

背景：肿瘤蛋白 p63 已被证明在慢性鼻窦炎伴鼻息肉 (CRSwNP) 的发展过程中对上皮功能障碍很重要，包括上皮屏障缺陷和粘膜炎症。Basonuclin1 (BNC1) 是一种上皮特异性转录因子，是 p63 的直接下游靶标，因此可能参与 CRSwNP 的发病机制。目的：我们试图调查 BNC1 是否与 CRSwNP 中 p63 介导的上皮屏障缺陷和鼻粘膜炎症有关。方法：鼻组织活检取自 91 名 CRSwNP 患者、49 名无鼻息肉的慢性鼻窦炎 (CRSsNP) 患者和 28 名对照受试者。免疫组织化学和免疫荧光染色分别用于确定 BNC1 在组织中的分布和在细胞中的定位。进行定量PCR以检测BNC1、TP63、上皮屏障蛋白和2型辅助T细胞炎症相关基因的表达水平。结果：与 CRSsNP（1.96 倍，p = 0.0003）和对照组（2.40 倍，p #x3c；0.0001）相比，CRSwNP 患者组织中BNC1 mRNA 表达显着升高。BNC1染色在鼻上皮中呈强阳性，并与 p63 阳性上皮细胞共定位。的表达BNC1 mRNA的强烈相关TP63 mRNA水平无论在组织活检（[R = 0.78，p＃X3C; 0.0001）和上皮刮出（[R = 0.97，p＃X3C; 0.0001）。BNC1表达也与正上皮屏障蛋白基因（相关CDH1，CLDN1，CLDN4，TJP1，和TJP2 T中涉及）和上皮基因_ħ 2炎症（IL33，CCL26、CLC和ALOX15 )。结论： BNC1 的过表达可能与TP63 的表达增加有关，并可能导致CRSwNP 中的上皮屏障缺陷和 T _H 2 炎症。
Int Arch 过敏免疫