BRF2在慢性鼻-鼻窦炎伴鼻息肉发病过程中的作用研究

doi:10.6040/j.issn.1673-3770.0.2018.068

摘要/Abstract

摘要： 目的研究BRF2在慢性鼻-鼻窦炎伴鼻息肉中的表达及意义。方法收集山东大学第二医院耳鼻咽喉头颈外科2016至2017年慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)手术标本37例及单纯鼻中隔偏曲手术标本18例,采用免疫荧光染色检测BRF2在慢性鼻-鼻窦炎伴鼻息肉组织中的表达及定位;脂多糖(LPS)刺激体外培养人鼻黏膜上皮细胞后,采用免疫荧光检测BRF2在细胞中的表达及定位,Western bloting及实时荧光定量PCR检测BRF2和内质网应激相关蛋白GRP78在细胞中的表达。结果 BRF2在慢性鼻-鼻窦炎伴鼻息肉组织中表达量上调并在胞浆中的分布增多;在体外,LPS刺激可诱导鼻黏膜上皮细胞中BRF2表达上调并在胞浆中的分布增多,并发现内质网应激相关蛋白GRP78表达上升。结论 BRF2可能介导了内质网应激,从而参与了慢性鼻-鼻窦炎伴鼻息肉的发病过程。

关键词: 鼻-鼻窦炎, 鼻息肉, BRF2, GRP78, 人鼻黏膜上皮细胞, 慢性

Abstract: Objective To study the expression and significance of BRF2 in chronic rhinosinusitis with nasal polyps. Methods 37 surgical specimens of chronic rhinosinusitis with nasal polyps(CRSwNP)and 18 surgical specimens of simple deviation of nasal septum were collected from 2016 to 2017 in the Department of Otorhinolaryngology Head and Neck Surgery, Second Hospital of Shandong University. Immunofluorescence staining was used to detect the expression and localization of BRF2 in chronic rhinosinusitis with nasal polyps. After cultured human nasal mucosa epithelial cells were stimulated with Llipopolysaccharides(LPS)in vitro, the expression and localization of BRF2 in cells were detected by immunofluorescence staining. Western blotting and quantitative real-time PCR were used to detect the expression of BRF2 and the endoplasmic reticulum stress-related protein GRP78 in cells. Results The expression of BRF2 in chronic rhinosinusitis with nasal polyps was up-regulated in whole cells and was particularly increased in the cytoplasm fraction. In vitro, LPS stimulation can induce the up-regulation of expression of BRF2 to be up-regulated in nasal mucosal epithelial cells and increase the distribution of BRF2 in the cytoplasm, and tThe expression of endoplasmic reticulum stress-related protein GRP78 was also increased. Conclusion BRF2 may mediate endoplasmic reticulum stress, which is involved in the pathogenesis of chronic rhinosinusitis with nasal polyps.

Key words: Human nasal epithelial cells, BRF2, GRP78, Nasal polyps, Rhinosinusitis, chronic

中图分类号:

R765.4+1

甘彬,张永举,许安廷. BRF2在慢性鼻-鼻窦炎伴鼻息肉发病过程中的作用研究[J]. 山东大学耳鼻喉眼学报, 2018, 32(3): 47-53.

GAN Bin, ZHANG Yongju, XU Anting. BRF2 in the pathogenesis of chronic rhinosinusitis with nasal polyps[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2018, 32(3): 47-53.

参考文献

[1] Akdis CA, Bachert C, Cingi C, et al. Endotypes and phenotypes of chronic rhinosinusitis: a PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology[J]. J Allergy Clin Immunol, 2013, 131(6): 1479-90.
[2] Mu(~overn)oz-Del-Castillo F, Jurado-Ramos A, Soler R, et al. Fungal sensitization in nasal polyposis[J]. J Investig Allergol Clin Immunol, 2009, 19(1): 6-12.
[3] Cabarcas S, Schramm L. RNA polymerase III transcription in cancer: the BRF2 connection[J]. Mol Cancer, 2011. 10: 47.
[4] Moreno-Moya JM, Vilella F, Simón C. MicroRNA: key gene expression regulators[J]. Fertil Steril, 2014, 101(6): 1516-1523.
[5] Lockwood WW, Chari R, Coe BP, et al. Integrative genomic analyses identify BRF2 as a novel lineage-specific oncogene in lung squamous cell carcinoma[J]. PLoS Med, 2010, 7(7): e1000315.
[6] Cabarcas S, Jacob J, Veras I, Schramm L. Differential expression of the TFIIIB subunits Brf1 and Brf2 in cancer cells[J]. BMC Mol Biol, 2008, 9: 74.
[7] Gullo F, Ceriani M, D'Aloia A, et al. Plant polyphenols and exendin-4 prevent hyperactivity and TNF-α release in LPS-treated in vitro neuron/astrocyte/microglial networks[J]. Front Neurosci, 2017, 11: 500.
[8] Shao L, Liu X, Zhu S, et al. The role of smurf1 in neuronal necroptosis after lipopolysaccharide-induced neuroinflammation[J]. Cell Mol Neurobiol, 2017. DOI:10.1007/s10571-017-0553-6.
[9] Lee S, Lee D, Jang TS, et al. Anti-inflammatory phenolic metabolites from the edible fungus phellinus baumii in LPS-stimulated RAW264.7 cells[J]. Molecules, 2017, 22(10). pii: E1583. DOI: 10.3390/molecules22101583
[10] Gaut JR, Hendershot LM. The modification and assembly of proteins in the endoplasmic reticulum[J]. Curr Opin Cell Biol, 1993, 5(4): 589-595.
[11] Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease[J]. Cell, 2010, 140(6): 900-917.
[12] Appenzeller-Herzog C, Hall MN. Bidirectional crosstalk between endoplasmic reticulum stress and mTOR signaling[J]. Trends Cell Biol, 2012, 22(5): 274-82.
[13] Ozcan L, Tabas I. Calcium signalling and ER stress in insulin resistance and atherosclerosis[J]. J Intern Med, 2016, 280(5): 457-464.
[14] Xiang C, Wang Y, Zhang H, et al. The role of endoplasmic reticulum stress in neurodegenerative disease[J]. Apoptosis, 2017, 22(1): 1-26.
[15] Zhang K, Kaufman RJ. From endoplasmic-reticulum stress to the inflammatory response[J]. Nature, 2008, 454(7203): 455-62.
[16] Malhotra JD, Miao H, Zhang K, et al. Antioxidants reduce endoplasmic reticulum stress and improve protein secretion[J]. Proc Natl Acad Sci U S A, 2008, 105(47): 18525-18530.
[17] Gouge J, Satia K, Guthertz N, et al. Redox signaling by the RNA polymerase III TFIIB-related factor Brf2[J]. Cell, 2015, 163(6): 1375-87.
[18] Guo H, Cui H, Peng X, et al. Nickel chloride(NiCl2)induces endoplasmic reticulum(ER)stress by activating UPR pathways in the kidney of broiler chickens[J]. Oncotarget, 2016, 7(14): 17508-17519.
[19] Lund VJ, Kennedy DW. Staging for rhinosinusitis[J]. Otolaryngol Head Neck Surg,1997, 117(3 Pt 2): 35-40.
[20] 鲁铭, 田辉, 李树海, 等. BRF2基因在食管鳞状细胞癌组织中的表达及其临床意义[J]. 中国肿瘤生物治疗杂志, 2012, 19(2): 175-179. LU Ming, TIAN Hui, LI Shuhai, et al. BRF2 gene expression in esophageal squamous cell carcinoma tissues and its clinical significance[J]. Chin J Cancer Biother, 2012, 19(2): 175-179.
[21] Tian Y, Lu M, Yue W, et al. TFIIB-related factor 2 is associated with poor prognosis of nonsmall cell lung cancer patients through promoting tumor epithelial-mesenchymal transition[J]. Biomed Res Int, 2014, 2014: 530786.
[22] Lu M, Tian H, Yue W, et al. TFIIB-related factor 2 over expression is a prognosis marker for early-stage non-small cell lung cancer correlated with tumor angiogenesis[J]. PLoS One, 2014, 9(2): e88032.

相关文章 15

[1]	冯思聪,于晓岚,娄丹. 基于囊泡组织Ki67、GM-CSF表达评估Messerklinger中鼻甲成形术对慢性鼻-鼻窦炎合并鼻息肉的效果[J]. 山东大学耳鼻喉眼学报, 2026, 40(3): 31-39.
[2]	翟雪纯,边欣,陈敬彩,邓家钰,叶子,杨萍丽. 慢性额窦炎患者焦虑抑郁特点及横断面研究[J]. 山东大学耳鼻喉眼学报, 2026, 40(2): 35-43.
[3]	吉睿,刘雅洁,王佳琪,史雅文,张炜明,殷敏. 慢性间歇性缺氧对大鼠茎突舌肌的影响及作用机制[J]. 山东大学耳鼻喉眼学报, 2026, 40(2): 44-48.
[4]	段思妤,薛金梅. 组蛋白去乙酰化酶2在慢性气道炎症性疾病糖皮质激素抵抗中的研究进展[J]. 山东大学耳鼻喉眼学报, 2026, 40(1): 120-126.
[5]	李阳松,袁发洋,杨艳,张田,喻国冻. 基于Web of Science进行生物制剂治疗慢性鼻窦炎文献计量学分析[J]. 山东大学耳鼻喉眼学报, 2025, 39(6): 54-64.
[6]	杜康丽,郑振宇,徐战将,张宇,陈露,卢梦垚. 鼻中隔偏曲并发慢性鼻窦炎风险预测模型的构建与验证[J]. 山东大学耳鼻喉眼学报, 2025, 39(6): 78-86.
[7]	熊琴, 张砚, 乌日娜, 李锋, 唐力行. 鼻用糖皮质激素在儿童中的应用[J]. 山东大学耳鼻喉眼学报, 2025, 39(6): 160-167.
[8]	张家齐,袁野,洪陈,顾敏,程雷,陆美萍. 基于孟德尔随机化的肠道菌群与慢性鼻窦炎鼻息肉的因果关系及代谢物中介研究[J]. 山东大学耳鼻喉眼学报, 2025, 39(5): 49-60.
[9]	董雪林,张治军. 掩蔽声治疗慢性主观性耳鸣的焦虑抑郁状态分析[J]. 山东大学耳鼻喉眼学报, 2025, 39(2): 18-24.
[10]	张广玲,陈兴雪,武天义,孙占伟,王卫卫,李世超,王广科. Tespa1在慢性鼻窦炎伴鼻息肉中的表达及作用研究[J]. 山东大学耳鼻喉眼学报, 2025, 39(2): 35-42.
[11]	曹正勇,李小波. 慢性鼻-鼻窦炎合并哮喘术后短程局部使用糖皮质激素辅助治疗的安全性和有效性[J]. 山东大学耳鼻喉眼学报, 2025, 39(2): 43-50.
[12]	周荷青,申琪. 中医药治疗变应性鼻炎疗效的生物标志物研究进展[J]. 山东大学耳鼻喉眼学报, 2025, 39(2): 168-176.
[13]	郭振平,李雪冰. 慢性主观性耳鸣患者心理特征、睡眠质量调查及与临床效果相关性[J]. 山东大学耳鼻喉眼学报, 2025, 39(1): 1-7.
[14]	王文晴,张丹,朱梦迪,王路阳,杨培培,孙思思,张秋敏,周慧. 慢性鼻窦炎伴鼻息肉复发手术时临床及组织病理学特征变化[J]. 山东大学耳鼻喉眼学报, 2025, 39(1): 46-53.
[15]	王奥维,时文杰. CRSwNP中医证型与TFH细胞相关因子的相关性研究[J]. 山东大学耳鼻喉眼学报, 2025, 39(1): 54-60.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed