前列腺源性ETS因子在哮喘及鼻黏膜炎性疾病中的研究进展

doi:10.6040/j.issn.1673-3770.0.2020.498

摘要/Abstract

摘要： 含SAM尖端结构域的E26转化特异性因子(SPDEF)是ETS转录因子家族的最新成员之一, SPDEF又称为前列腺源性ETS因子(PDEF),首次发现其在前列腺癌中高度表达,参与肿瘤细胞的增殖分化、迁移凋亡和血管形成。近年来研究发现SPDEF与杯状细胞增生和分化密切相关,是调控呼吸道黏液高分泌的核心因子。对SPDEF调控黏液高分泌的机制及其在呼吸道慢性炎性疾病中的研究进展做一综述,以期为呼吸道黏液高分泌疾病的发病机制和诊治提供新思路。

关键词: 前列腺源性ETS因子, 杯状细胞化生, 黏液高分泌, 气道炎症, 慢性鼻-鼻窦炎, 变应性鼻炎, 哮喘

Abstract: The SAM pointed domain-containing ETS transcription factor(SPDEF), a new member of the E26 transformation-specific(ETS)transcription factor family, SPDEF is also known as prostate-derived ETS factor(PDEF),has been found, for the first time, to be highly expressed in prostate tumor cells and involved in cell proliferation, differentiation, migration, apoptosis, and angiogenesis. Recently, some scholars found that SPDEF is related to the proliferation and differentiation of goblet cells, and it is the core factor that regulates the hypersecretion of the respiratory tract mucus. This article mainly reviews the mechanism underlying the regulation of mucus hypersecretion by SPDEF and the research progress on its involvement in chronic airway inflammatory diseases to provide new insights into the pathogenesis, diagnosis, and treatment of respiratory mucus hypersecretion diseases.

Key words: Prostate-derived ETS factor, Goblet cell metaplasia, Mucus hypersecretion, Airway inflammation, Chronic rhinosinusitis, AR, Asthma

中图分类号:

R765.25

王娜,柴向斌. 前列腺源性ETS因子在哮喘及鼻黏膜炎性疾病中的研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 136-141.

WANG Na,CHAI Xiangbin. Research progress on prostate-derived ETS factor in asthma and inflammatory diseases of the nasal mucosa[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(3): 136-141.

参考文献

[1] Bai J, Miao BP, Wu XM, et al. Enhanced expression of SAM-pointed domain-containing Ets-like factor in chronic rhinosinusitis with nasal polyps[J]. Laryngoscope, 2015, 125(3): E97-E103. doi:10.1002/lary.25008.
[2] 龙锐, 李娟, 周远大. 变应性鼻炎黏液高分泌的药物治疗新进展[J]. 中国临床药理学杂志, 2017, 33(8): 760-763,767. doi:10.13699/j.cnki.1001-6821.2017.08.024. LONG Rui, LI Juan, ZHOU Yuanda. New progress of pharmacotherapy on mucus hypersecretion in allergic rhinitis[J]. Chin J Clin Pharmacol, 2017, 33(8): 760-763,767. doi:10.13699/j.cnki.1001-6821.2017.08.024.
[3] Korfhagen TR, Kitzmiller J, Chen G, et al. SAM-pointed domain ETS factor mediates epithelial cell-intrinsic innate immune signaling during airway mucous Metaplasia[J]. PNAS, 2012, 109(41): 16630-16635. doi:10.1073/pnas.1208092109.
[4] Carrer M, Crosby JR, Sun GZ, et al. Antisense oligonucleotides targeting jagged 1 reduce house dust mite-induced goblet cell Metaplasia in the adult murine lung[J]. Am J Respir Cell Mol Biol, 2020, 63(1): 46-56. doi:10.1165/rcmb.2019-0257OC.
[5] Curran DR, Cohn L. Advances in mucous cell Metaplasia[J]. Am J Respir Cell Mol Biol, 2010, 42(3): 268-275. doi:10.1165/rcmb.2009-0151tr.
[6] Rajavelu P, Chen G, Xu Y, et al. Airway epithelial SPDEF integrates goblet cell differentiation and pulmonary Th2 inflammation[J]. J Clin Invest, 2015, 125(5): 2021-2031. doi:10.1172/jci79422.
[7] Park KS, Korfhagen TR, Bruno MD, et al. SPDEF regulates goblet cell hyperplasia in the airway epithelium[J]. J Clin Invest, 2007, 117(4): 978-988. doi:10.1172/jci29176.
[8] Chen G, Korfhagen TR, Xu Y, et al. SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production[J]. J Clin Invest, 2009, 119(10): 2914-2924. doi:10.1172/JCI39731.
[9] Oettgen P, Finger E, Sun ZJ, et al. PDEF, a novel prostate epithelium-specific ets transcription factor, interacts with the androgen receptor and activates prostate-specific antigen gene expression[J]. J Biol Chem, 2000, 275(2): 1216-1225. doi:10.1074/jbc.275.2.1216.
[10] Cho JY, Lee M, Ahn JM, et al. Proteomic analysis of a PDEF Ets transcription factor-interacting protein complex[J]. J Proteome Res, 2009, 8(3): 1327-1337. doi:10.1021/pr800683b.
[11] Noah TK, Kazanjian A, Whitsett J, et al. SAM pointed domain ETS factor(SPDEF)regulates terminal differentiation and maturation of intestinal goblet cells[J]. Exp Cell Res, 2010, 316(3): 452-465. doi:10.1016/j.yexcr.2009.09.020.
[12] Situ J, Zhang H, Lu L, et al. Clinical significance of PSMA, TERT and PDEF in malignant tumors of the prostate[J]. Eur Rev Med Pharmacol Sci, 2017, 21(15): 3347-3352.
[13] Guo M, Tomoshige K, Meister M, et al. Gene signature driving invasive mucinous adenocarcinoma of the lung[J]. EMBO Mol Med, 2017, 9(4): 462-481. doi:10.15252/emmm.201606711.
[14] Wu J, Qin W, Wang Y, et al. SPDEF is overexpressed in gastric cancer and triggers cell proliferation by forming a positive regulation loop with FoxM1[J]. J Cell Biochem, 2018, 119(11): 9042-9054. doi:10.1002/jcb.27161.
[15] McCauley HA, Guasch G. Three cheers for the goblet cell: maintaining homeostasis in mucosal epithelia[J]. Trends Mol Med, 2015, 21(8): 492-503. doi:10.1016/j.molmed.2015.06.003.
[16] Rock JR, Gao X, Xue Y, et al. Notch-dependent differentiation of adult airway basal stem cells[J]. Cell Stem Cell, 2011, 8(6): 639-648. doi:10.1016/j.stem.2011.04.003.
[17] Doherty T, Broide D. Cytokines and growth factors in airway remodeling in asthma[J]. Curr Opin Immunol, 2007, 19(6): 676-680. doi:10.1016/j.coi.2007.07.017.
[18] Tyner JW, Kim EY, Ide K, et al. Blocking airway mucous cell Metaplasia by inhibiting EGFR antiapoptosis and IL-13 transdifferentiation signals[J]. J Clin Invest, 2006, 116(2): 309-321. doi:10.1172/jci25167.
[19] Song J, Cano-Rodriquez D, Winkle M, et al. Targeted epigenetic editing of SPDEF reduces mucus production in lung epithelial cells[J]. Am J Physiol Lung Cell Mol Physiol, 2017, 312(3): L334-L347. doi:10.1152/ajplung.00059.2016.
[20] Hoshino M, Morita S, Iwashita H, et al. Increased expression of the human Ca²⁺-activated Cl- channel 1(CaCC1)gene in the asthmatic airway[J]. Am J Respir Crit Care Med, 2002, 165(8): 1132-1136. doi:10.1164/ajrccm.165.8.2107068.
[21] Yu H, Li Q, Kolosov VP, et al. Interleukin-13 induces mucin 5AC production involving STAT6/SPDEF in human airway epithelial cells[J]. Cell Commun Adhes, 2010, 17(4/5/6): 83-92. doi:10.3109/15419061.2010.551682.
[22] 程丹, 陈恒睿, 王梦玫, 等. 白细胞介素-13对人支气管上皮细胞SPDEF表达的影响及SPDEF在哮喘气道黏液高分泌中的作用[J]. 临床内科杂志, 2020, 37(1): 53-56. doi:10.3969/j.issn.1001-9057.2020.01.016. CHENG Dan, CHEN Hengrui, WANG Mengmei, et al. Effects of interleukin-13 on SPDEF expression in human bronchial epithelial cells and role of SPDEF in airway mucus hypersecretion of asthma[J]. J Clin Intern Med, 2020, 37(1): 53-56. doi:10.3969/j.issn.1001-9057.2020.01.016.
[23] Marko CK, Menon BB, Chen G, et al. Spdef null mice lack conjunctival goblet cells and provide a model of dry eye[J]. Am J Pathol, 2013, 183(1): 35-48. doi:10.1016/j.ajpath.2013.03.017.
[24] Chen G, Korfhagen TR, Karp CL, et al. Foxa3 induces goblet cell Metaplasia and inhibits innate antiviral immunity[J]. Am J Respir Crit Care Med, 2014, 189(3): 301-313. doi:10.1164/rccm.201306-1181oc.
[25] Schroeder BW, Verhaeghe C, Park SW, et al. AGR2 is induced in asthma and promotes allergen-induced mucin overproduction[J]. Am J Respir Cell Mol Biol, 2012, 47(2): 178-185. doi:10.1165/rcmb.2011-0421oc.
[26] Chen G, Volmer AS, Wilkinson KJ, et al. Role of spdef in the regulation of Muc5b expression in the airways of naive and mucoobstructed mice[J]. Am J Respir Cell Mol Biol, 2018, 59(3): 383-396. doi:10.1165/rcmb.2017-0127oc.
[27] Morcillo EJ, Cortijo J. Mucus and MUC in asthma[J]. Curr Opin Pulm Med, 2006, 12(1): 1-6. doi:10.1097/01.mcp.0000198064.27586.37.
[28] Ren X, Shah TA, Ustiyan V, et al. FOXM1 promotes allergen-induced goblet cell Metaplasia and pulmonary inflammation[J]. Mol Cell Biol, 2013, 33(2): 371-386. doi:10.1128/mcb.00934-12.
[29] 仲秀华, 曾晓宁. SPDEF在气道上皮杯状细胞化生中的作用[J]. 南京医科大学学报(自然科学版), 2019, 39(4): 614-618. ZHONG Xiuhua, ZENG Xiaoning. Role of SPDEF in the regulation of goblet cell Metaplasia of airway epithelium[J]. J Nanjing Medicial Univ, 2019, 39(4): 614-618.
[30] Shi N, Zhang J, Chen SY. Runx2, a novel regulator for goblet cell differentiation and asthma development[J]. FASEB J, 2017, 31(1): 412-420. doi:10.1096/fj.201600954R.
[31] 张宇,宋西成.慢性鼻窦炎伴鼻息肉与哮喘的相关性机制及治疗策略研究进展[J].山东大学耳鼻喉眼学报,2019, 33(1): 49-52. doi: 10.6040/j.issn.1673-3770.1.2018.033. ZHANG Yu, SONG Xicheng. Advances in interaction mechanisms and treatment strategy between chronic rhinosinusitis w ith nasal polyp and asthma[J]. J Otolaryngol Ophthalmol Shandong Univ, 2019, 33(1): 49-52. doi:10.6040/j.issn.1673-3770.1.2018.033.
[32] Martínez-Rivera C, Crespo A, Pinedo-Sierra C, et al. Mucus hypersecretion in asthma is associated with rhinosinusitis, polyps and exacerbations[J]. Respir Med, 2018, 135: 22-28. doi:10.1016/j.rmed.2017.12.013.
[33] Licari A, Brambilla I, de Filippo M, et al. The role of upper airway pathology as a co-morbidity in severe asthma[J]. Expert Rev Respir Med, 2017, 11(11): 855-865. doi:10.1080/17476348.2017.1381564.
[34] Kuperman DA, Huang XZ, Koth LL, et al. Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma[J]. Nat Med, 2002, 8(8): 885-889. doi:10.1038/nm734.
[35] SUN LiFeng, REN XiaoMeng, WANG I-Ching, et al. The FOXM1 inhibitor RCM-1 suppresses goblet cell metaplasia and prevents IL-13 and STAT6 signaling in allergen-exposed mice[J]. Sci Signal, 2017, 10: 275. doi: 10.1126/scisignal.aai8583.
[36] Kuyper LM, Paré PD, Hogg JC, et al. Characterization of airway plugging in fatal asthma[J]. Am J Med, 2003, 115(1): 6-11. doi:10.1016/s0002-9343(03)00241-9.
[37] Martínez-Antón A, de Bolós C, Alobid I, et al. Corticosteroid therapy increases membrane-tethered while decreases secreted mucin expression in nasal polyps[J]. Allergy, 2008, 63(10): 1368-1376. doi:10.1111/j.1398-9995.2008.01678.x.
[38] Liu ZE, Han B, Chen X, et al. Pycnogenol ameliorates asthmatic airway inflammation and inhibits the function of goblet cells[J]. DNA Cell Biol, 2016, 35(11): 730-739. doi:10.1089/dna.2016.3264.
[39] Nagashima A, Shinkai M, Shinoda M, et al. Clarithromycin suppresses chloride channel accessory 1 and inhibits interleukin-13-induced goblet cell hyperplasia in human bronchial epithelial cells[J]. Antimicrob Agents Chemother, 2016, 60(11): 6585-6590. doi:10.1128/aac.01327-16.
[40] Liu Cong-Lin, Shi Guo-Ping, Calcium-activated chloride channel regulator 1(CLCA1): More than a regulator of chloride transport and mucus production[J]. World Allergy Organ J, 2019, 12: 100077. doi:10.1016/j.waojou.2019.100077
[41] Jha A, Thwaites RS, Tunstall T, et al. Increased nasal mucosal interferon and CCL13 response to a TLR7/8 agonist in asthma and allergic rhinitis[J]. J Allergy Clin Immunol, 2021, 147(2): 694-703.e12. doi:10.1016/j.jaci.2020.07.012.
[42] Yang T, Luo Q, Feng K, et al. Expression of Foxm1 in chronic sinusitis and itsrelationship with MUC5AC[J]. Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi, 2016, 30(13): 1053-1057. doi:10.13201/j.issn.1001-1781.2016.13.012.
[43] Li FY, Yin RL, Guo Q. Circulating angiopoietin-2 and the risk of mortality in patients with acute respiratory distress syndrome: a systematic review and meta-analysis of 10 prospective cohort studies[J]. Ther Adv Respir Dis, 2020, 14: 1753466620905274. doi:10.1177/1753466620905274.

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