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染色质重塑复合物 SWI/SNF 和 VDR 在慢性鼻-鼻窦炎中的作用。

Role of chromatin remodeling complex SWI/SNF and VDR in chronic rhinosinusitis.

机构信息

Department of Otorhinolaryngology, Faculty of Medicine and Dentistry, Medical University of Warsaw, Poland.

Department of Molecular and Translational Oncology, Maria Skłodowska-Curie Institute Oncology Center, Warszawa, Poland.

出版信息

Adv Clin Exp Med. 2020 Mar;29(3):313-323. doi: 10.17219/acem/117683.

Abstract

BACKGROUND

The SWI/SNF (SWItch/sucrose non-fermentable) chromatin remodeling complex enables glucocorticoid receptor (GR) and vitamin D receptor (VDR) to function correctly and is engaged in inflammation response. The SWI/SNF may play an important role in chronic rhinosinusitis (CRS).

OBJECTIVES

The aim of this study was to assess the following: 1) the gene and protein expression of the SWI/SNF complex subunits in sinonasal mucosa; 2) relation of SWI/SNF complex and VDR expression; and 3) correlation with clinical data.

MATERIAL AND METHODS

The study population consisted of 52 subjects with CRS without nasal polyps, 55 with CRS with nasal polyps and 59 controls. The SWI/SNF protein expression level was analyzed in immunohistochemical (IHC) staining. Human nasal epithelial cells (HNECs) was stimulated using lipopolysaccharide (LPS), Staphylococcal enterotoxin B (SEB) and vitamin D3 (vitD3) in vitro. The transcript level of the SWI/SNF subunits was measured with polymerase chain reaction (PCR).

RESULTS

In the control group, the intensity of the IHC staining for SWI/SNF subunits was significantly higher than in both groups of patients with CRS (p < 0.05). A positive correlation of the SWI/SNF protein expression was noticed with VDR expression level (p < 0.043). Association between SWI/SNF protein expression level and allergy, neutrophils and body mass index (BMI) has been observed (p < 0.05). The decreased transcript level of the SWI/SNF subunits genes in HNECs was observed after LPS stimulation and increased after vitD3 stimulation.

CONCLUSIONS

The SWI/SNF complex may influence CRS through steroid hormone signaling and VDR. Thus, modification in therapy may be mandatory in patients with CRS and altered SWI/SNF signaling, reflecting resistance to steroids treatment.

摘要

背景

SWI/SNF(切换/蔗糖非发酵)染色质重塑复合物使糖皮质激素受体(GR)和维生素 D 受体(VDR)能够正常发挥作用,并参与炎症反应。SWI/SNF 可能在慢性鼻鼻窦炎(CRS)中发挥重要作用。

目的

本研究旨在评估以下内容:1)鼻黏膜中 SWI/SNF 复合物亚基的基因和蛋白表达;2)SWI/SNF 复合物与 VDR 表达的关系;3)与临床资料的相关性。

材料和方法

研究人群包括 52 例无鼻息肉的 CRS 患者、55 例有鼻息肉的 CRS 患者和 59 例对照者。采用免疫组织化学(IHC)染色分析 SWI/SNF 蛋白表达水平。体外用人鼻上皮细胞(HNECs)用脂多糖(LPS)、葡萄球菌肠毒素 B(SEB)和维生素 D3(vitD3)刺激。用聚合酶链反应(PCR)测量 SWI/SNF 亚基的转录水平。

结果

在对照组中,SWI/SNF 亚基的 IHC 染色强度明显高于 CRS 两组患者(p<0.05)。SWI/SNF 蛋白表达与 VDR 表达水平呈正相关(p<0.043)。SWI/SNF 蛋白表达水平与过敏、中性粒细胞和体重指数(BMI)之间存在关联(p<0.05)。LPS 刺激后观察到 HNECs 中 SWI/SNF 亚基基因的转录水平降低,vitD3 刺激后增加。

结论

SWI/SNF 复合物可能通过甾体激素信号和 VDR 影响 CRS。因此,在 SWI/SNF 信号转导改变的 CRS 患者中,改变治疗方法可能是必要的,这反映了对类固醇治疗的耐药性。

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