变应性鼻炎相关转录因子:SP1加重鼻上皮屏障损伤。

IF 3.4 3区 医学 Q2 IMMUNOLOGY
Zhaohui Shi, Tianfeng Zhao, Yongjin Wu, Zhiyuan Tang, Zaixing Wang, Dingbo Li, Chong Wang
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引用次数: 0

摘要

过敏性鼻炎(AR)是一种以炎症和屏障功能障碍为特征的呼吸道疾病。转录因子特异性蛋白1 (SP1)是Sp/ kr ppel样因子家族的一员,已知与炎症有关。本研究旨在探讨SP1对AR的影响。通过多次鼻内注射卵清蛋白(OVA)建立了AR小鼠模型。在气液界面(ALI)培养人鼻上皮细胞(HNEpCs),并用IL-13处理形成屏障损伤的细胞模型。生物信息样本显示,SP1在AR患者鼻上皮细胞中表达上调,在AR小鼠鼻黏膜中也有高表达。沉默Sp1减少了AR小鼠的鼻部摩擦、打喷嚏、血清IgE水平、组胺水平和鼻肿胀。此外,Sp1沉默抑制杯状细胞增殖、嗜酸性粒细胞浸润以及IL-4和IL-13水平。Sp1敲除逆转了异硫氰酸-葡聚糖4kda通透性升高、鼻上皮细胞脱落以及E-cadherin和cludin -1表达降低。在体外,敲除SP1导致上皮电阻值和E-cadherin和Claudin-1水平的增加。机制上,SP1通过转录活性上调叉头盒C1 (FOXC1)表达,FOXC1过表达逆转了SP1沉默对上皮屏障损伤的保护作用。总的来说,我们的研究结果表明SP1加重了AR,可能是通过SP1对FOXC1的转录激活。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Associated transcription factors of allergic rhinitis: SP1 aggravates nasal epithelial barrier damage.

Allergic rhinitis (AR) is a respiratory airway disorder characterized by inflammation and barrier dysfunction. The transcription factor specificity protein 1 (SP1), a member of the Sp/Krüppel-like factor family, is known to be associated with inflammation. This study aimed to explore the impacts of SP1 on AR. An AR murine model was developed through multiple intranasal challenges with ovalbumin (OVA). Human nasal epithelial cells (HNEpCs) were cultured at the air-liquid interface (ALI) and treated with IL-13 to create a cell model with barrier damage. Bioinformation samples revealed that SP1 expression was upregulated in nasal epithelial cells of people with AR. High Sp1 expression was observed in AR mice nasal mucosa. Silencing Sp1 reduced nasal rubbing, sneezing, serum levels of IgE, histamine, and nasal swelling in AR mice. Additionally, Sp1 silencing inhibited goblet cell proliferation, eosinophilic infiltration, and levels of IL-4 and IL-13. Sp1 knockdown reversed the elevated fluorescein isothiocyanate-dextran 4 kDa permeability, nasal epithelial cell shedding, and decreased expression of E-cadherin and Claudin-1. In vitro, knocking down SP1 led to an increase in transepithelial electrical resistance and levels of E-cadherin and Claudin-1. Mechanistically, SP1 upregulated forkhead box C1 (FOXC1) expression through transcriptional activity, and FOXC1 overexpression reversed the protective effects of SP1 silencing on epithelial barrier damage. Overall, our findings suggest that SP1 aggravates AR, potentially through the transcriptional activation of SP1 to FOXC1.

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来源期刊
Journal of immunology
Journal of immunology 医学-免疫学
CiteScore
8.20
自引率
2.30%
发文量
495
审稿时长
1 months
期刊介绍: The JI publishes novel, peer-reviewed findings in all areas of experimental immunology, including innate and adaptive immunity, inflammation, host defense, clinical immunology, autoimmunity and more. Special sections include Cutting Edge articles, Brief Reviews and Pillars of Immunology. The JI is published by The American Association of Immunologists (AAI)
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