基质金属蛋白酶及抑制剂、转化生长因子β1对慢性鼻-鼻窦炎组织重塑的机制研究

常雪岩; 周凌

doi:10.16766/j.cnki.issn.1674-4152.002736

基质金属蛋白酶及抑制剂、转化生长因子β1对慢性鼻-鼻窦炎组织重塑的机制研究

doi: 10.16766/j.cnki.issn.1674-4152.002736

常雪岩¹,
周凌^2, ,

1.
黑龙江中医药大学研究生院，黑龙江哈尔滨 150040
2.
黑龙江中医药大学附属第一医院耳鼻喉科, 黑龙江哈尔滨 150040

基金项目:

国家自然科学基金项目 8187152123

详细信息

通讯作者:
周凌, E-mail: zhouling8913@163.com

中图分类号: R765.21 R765.41
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- 被引次数: 0
出版历程
- 收稿日期: 2022-03-26
- 网络出版日期: 2022-12-30

Mechanism of matrix metalloproteinases and inhibitors, transforming growth factors β1 on the tissue remodelling in chronic rhinosinusitis

CHANG Xue-yan¹,
ZHOU Ling^{2
, ,}

1.
Graduate School of Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang 150040, China

摘要

摘要: 慢性鼻-鼻窦炎(chronic rhinosinusitis, CRS)常以鼻塞、流黏或脓涕、头痛等为主要临床表现，影响日常生活质量，且因其发病机制尚不明确，缺乏准确有效的治疗方法，患者常需进行反复或多种方法联合治疗，这造成了较大的心理负担和经济负担。组织重塑理论是国内外均已认可的慢性鼻-鼻窦炎发病的主要机理，其中细胞外基质(extracellular matrix，ECM)的生成和降解发生失衡是组织重塑的重要特点之一，而CRS不同亚型的组织重塑机理也并不相同，这是由于不同亚型中基质金属蛋白酶(matrix metalloproteinases，MMPs)及其抑制剂(tissue inhibitor of metalloproteinase，TIMPs)表达并不相同。基质金属蛋白酶及其抑制剂除单独影响ECM来参与CRS组织重塑，还通过其摩尔比值来影响ECM代谢以此参与CRS组织重塑。转化生长因子β1(transforming growth factor-β1，TGF-β1)除直接刺激各种通路及细胞因子来影响组织重塑，还可通过TGF-β1/Smad通路来影响ECM代谢，以此参与CRS组织重塑。本文对MMPs、TIMPs、TGF-β1结构及对CRS组织重塑的机制进行综述。
- 慢性鼻-鼻窦炎 /
- 基质金属蛋白酶 /
- 转化生长因子β1 /
- 组织重塑
Abstract: The main clinical manifestations of chronic rhinosinusitis (CRS) are nasal congestion, mucous or purulent discharge and headache, which affect quality of life. The pathogenesis of CRS is unclear and accurate and effective treatment methods are lacking. Repeated or combined treatments using multiple methods are needed, which impose large psychological and economic burden. Tissue remodelling theory is an important pathogenesis of CRS. The imbalance between the generation and degradation of extracellular matrix (ECM) is one of the important characteristics of tissue remodelling, and the tissue remodelling mechanisms of different subtypes of CRS are different because the expression levels of matrix metalloproteinases (MMPs) and the tissue inhibitor of metalloproteinases (TIMPs) vary by subtype. MMPs and their inhibitors not only affect the ECM but also affect ECM metabolism through molar ratio and participate in CRS tissue remodelling. Transforming growth factor-β1 (TGF-β1) in addition to directly stimulating various pathways and cytokines to affect tissue remodelling, it can also be used TGF-β1/Smad pathway to affect ECM metabolism, so as to participate in CRS tissue remodelling. MMPs, TIMPs and TGF-β1 structure and the mechanism of CRS tissue remodelling are reviewed.
- Chronic rhinosinusitis /
- Matrix metalloproteinases /
- Transforming growth factor-β1 /
- Tissue remodelling

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参考文献(44)

[1]	中华耳鼻咽喉头颈外科杂志编辑委员会鼻科组, 中华医学会耳鼻咽喉头颈外科学分会鼻科学组. 中国慢性鼻窦炎诊断和治疗指南(2018)[J]. 中华耳鼻咽喉头颈外科杂志, 2019, 54(2): 81-100. doi: 10.3760/cma.j.issn.1673-0860.2019.02.001 Subspecialty Group of Rhinology. Editorial Board of Chinese Journal of Otorhinolaryngology Head and Neck Surgery; Subspecialty Group of Rhinology. Society of Otorhinolaryngology Head and Neck Surgery. Chinese Medical Association. Chinese guidelines for diagnosis and treatment of chronic rhinosinusitis (2018)[J]. Chinese JOurnal of Otorhinolaryngology Head and Neck Surgery, 2019, 54(2): 81-100. doi: 10.3760/cma.j.issn.1673-0860.2019.02.001
[2]	YAO Y, XIE S M, YANG C G, et al. Biomarkers in the evaluation and management of chronic rhinosinusitis with nasal polyposis[J]. Eur Arch Otorhinolaryngol, 2017, 274(10): 3559-3566. doi: 10.1007/s00405-017-4547-2
[3]	孙立薇, 朱冬冬, 孟粹达. 慢性鼻窦炎的内型研究及临床应用[J]. 临床耳鼻咽喉头颈外科杂志, 2020, 34(8): 765-768. https://www.cnki.com.cn/Article/CJFDTOTAL-LCEH202008022.htm SUN L W, ZHU D D, MENG C D. The study and clinical application of the endotypes of chronic rhinosinusitis[J]. Journal of Clinical Otorhinolaryngology Head And Neck Surgery, 2020, 34(8): 765-768. https://www.cnki.com.cn/Article/CJFDTOTAL-LCEH202008022.htm
[4]	姚尧, 慕婷婷, 杨玉娟, 等. IL-36γ通过NF-κB通路调控慢性鼻窦炎伴鼻息肉组织重塑相关因子的表达[J]. 中国耳鼻咽喉头颈外科, 2021, 28(10): 613-617. https://www.cnki.com.cn/Article/CJFDTOTAL-EBYT202110004.htm YAO Y, MU T T, YANG Y J, et al. The effect of IL-36γon the expressions of tissue remodeling related factors in chronic rhinosinusitis with nasal polyps through NF-κB pathway[J]. Chinese Archives of Otolaryngology-Head and Neck Surgery, 2021, 28(10): 613-617. https://www.cnki.com.cn/Article/CJFDTOTAL-EBYT202110004.htm
[5]	MARTIN M J, GARCIA-SANCHEZ A, ESTRAVIS M, et al. Genetics and epigenetics of nasal polyposis: A systematic review[J]. J Investig Allergol Clin Immunol, 2021, 31(3): 196-211. doi: 10.18176/jiaci.0673
[6]	MUELLER S K. The Role of exosomes in the pathophysiology of chronic rhinosinusitis[J]. Front Cell Infect Microbiol, 2022, 11: 812920. DOI: 10.3389/fcimb.2021.812920.
[7]	RADAJEWSKI K, KALIÑCZAK-GÓRNA P, ZDRENKA M, et al. Short term pre-operative oral corticosteroids-tissue remodeling in chronic rhinosinusitis with nasal polyps[J]. J Clin Med, 2021, 10(15): 3346. doi: 10.3390/jcm10153346
[8]	LI M, KEENAN C R, LOPEZ-CAMPOS G, et al. A non-canonical pathway with potential for safer modulation of transforming growth factor-β1 in steroid-resistant airway diseases[J]. iScience, 2019, 12: 232-246. doi: 10.1016/j.isci.2019.01.023
[9]	TODD J L, VINISKO R, LIU Y, et al. Circulating matrix metalloproteinases and tissue metalloproteinase inhibitors in patients with idiopathic pulmonary fibrosis in the multicenter IPF-PRO Registry cohort[J]. BMC Pulm Med, 2020, 20(1): 64. doi: 10.1186/s12890-020-1103-4
[10]	刘明明, 李爱玲, 修瑞娟. 基质金属蛋白酶的研究进展[J]. 中国病理生理杂志, 2018, 34(10): 1914-1920. doi: 10.3969/j.issn.1000-4718.2018.10.029 LIU M M, LI A L, XIU R J. Research progress on matrix metalloproteinases[J]. Chinese Journal of Pathophysiology, 2018, 34(10): 1914-1920. doi: 10.3969/j.issn.1000-4718.2018.10.029
[11]	WU F, TIAN P, MA Y, et al. Reactive oxygen species are necessary for bleomycin A5-induced apoptosis and extracellular matrix elimination of nasal polyp-derived fibroblasts[J]. Ann Otol Rhinol Laryngol, 2019, 128(2): 135-144. doi: 10.1177/0003489418812905
[12]	UM J Y, LEE S A, PARK J H, et al. Role of adenosine monophosphate-activated protein kinase on cell migration, matrix contraction, and matrix metalloproteinase-1 and matrix metalloproteinase-2 production in nasal polyp-derived fibroblasts[J]. Am J Rhinol Allergy, 2017, 31(6): 357-363. doi: 10.2500/ajra.2017.31.4477
[13]	GUERRA G, TESTA D, SALZANO F A, et al. Expression of matrix metalloproteinases and their tissue inhibitors in chronic rhinosinusitis with nasal polyps: Etiopathogenesis and recurrence[J]. Ear Nose Throat J, 2021, 100(5_suppl): 597S-605S. doi: 10.1177/0145561319896635
[14]	KIM D K, JIN H R, EUN K M, et al. The role of interleukin-33 in chronic rhinosinusitis[J]. Thorax, 2017, 72(7): 635-645. doi: 10.1136/thoraxjnl-2016-208772
[15]	HUANG J C, CHEN X H, WANG Z Y, et al. Interleukin-17A expression correlated with the prognosis of chronic rhinosinusitis with nasal polyps and the anti-Interleukin-17A effect in a murine nasal polyps model[J]. ORL J Otorhinolaryngol Relat Spec, 2020, 82(5): 257-267. doi: 10.1159/000507865
[16]	BORUK M, RAILWAH C, LORA A, et al. Elevated S100A9 expression in chronic rhinosinusitis coincides with elevated MMP production and proliferation in vitro[J]. Sci Rep, 2020, 10(1): 16350. doi: 10.1038/s41598-020-73480-8
[17]	KIM B, LEE H J, IM N R, et al. Effect of matrix metalloproteinase inhibitor on disrupted E-cadherin after acid exposure in the human nasal epithelium[J]. Laryngoscope, 2018, 128(1): E1-E7. doi: 10.1002/lary.26932
[18]	李霞, 常利红, 黄子真, 等. IL-19及其受体与慢性鼻-鼻窦炎组织重塑的相关性研究[J]. 中国病理生理杂志, 2017, 33(5): 919-924. doi: 10.3969/j.issn.1000-4718.2017.05.025 LI X, CHANG L H, HUANG Z Z, et al. Correlation of IL-19 and its receptors with tissue remodeling in chronic rhinosinusitis[J]. Chinese Journal of Pathophysiology, 2017, 33(5): 919-924. doi: 10.3969/j.issn.1000-4718.2017.05.025
[19]	伯铭羽, 王向东, 王鸿, 等. 重塑相关因子在慢性鼻窦炎的表达[J]. 首都医科大学学报, 2013, 34(6): 785-789. https://www.cnki.com.cn/Article/CJFDTOTAL-SDYD201306002.htm BO M Y, WANG X D, WANG H, et al. Expression of remodeling associated factors in the tissue of chronic rhinosinusitis[J]. Journal of Capital Medical University, 2013, 34(6): 785-789. https://www.cnki.com.cn/Article/CJFDTOTAL-SDYD201306002.htm
[20]	MULUK N B, ARIKAN O K, ATASOY P, et al. The role of MMP-2, MMP-9, and TIMP-1 in the pathogenesis of nasal polyps: Immunohistochemical assessment at eight different levels in the epithelial, subepithelial, and deep layers of the mucosa[J]. Ear Nose Throat J, 2015, 94(4-5): E1-E13.
[21]	LI X Y, MENG J, QIAO X M, et al. Expression of TGF, matrix metalloproteinases, and tissue inhibitors in Chinese chronic rhinosinusitis[J]. J Allergy Clin Immunol, 2010, 125(5): 1061-1068. doi: 10.1016/j.jaci.2010.02.023
[22]	TSUDA T, NISHIDE M, MAEDA Y, et al. Pathological and therapeutic implications of eosinophil-derived semaphorin 4D in eosinophilic chronic rhinosinusitis[J]. J Allergy Clin Immunol, 2020, 145(3): 843-854. doi: 10.1016/j.jaci.2019.12.893
[23]	ZHANG Y Y, LOU H F, WANG Y, et al. Comparison of corticosteroids by 3 approaches to the treatment of chronic rhinosinusitis with nasal polyps[J]. Allergy Asthma Immunol Res, 2019, 11(4): 482-497. doi: 10.4168/aair.2019.11.4.482
[24]	TSUDA T, MAEDA Y, NISHIDE M, et al. Eosinophil-derived neurotoxin enhances airway remodeling in eosinophilic chronic rhinosinusitis and correlates with disease severity[J]. Int Immunol, 2019, 31(1): 33-40. doi: 10.1093/intimm/dxy061
[25]	FENG X, PAYNE S C, BORISH L, et al. Differential expression of extracellular matrix components in nasal polyp endotypes[J]. Am J Rhinol Allergy, 2019, 33(6): 665-670. doi: 10.1177/1945892419860634
[26]	LORDA-DIEZ C I, DUARTE-OLIVENZA C, HURLE J M, et al. Transforming growth factor beta signaling: The master sculptor of fingers[J]. Dev Dyn, 2022, 251(1): 125-136.
[27]	NARIKAWA M, UMEMURA M, TANAKA R, et al. Acute Hyperthermia inhibits TGF-β1-induced cardiac fibroblast activation via suppression of Akt signaling[J]. Sci Rep, 2018, 8(1): 6277. doi: 10.1038/s41598-018-24749-6
[28]	JIANG W X, ZHOU C, MA C X, et al. TGF-β1 induces epithelial-to-mesenchymal transition in chronic rhinosinusitis with nasal polyps through microRNA-182[J]. Asian Pac J Allergy Immunol, 2021. DOI: 10.12932/AP-040921-1224.
[29]	王彤, 臧洪瑞, 李云川, 等. Smad信号通路在慢性鼻-鼻窦炎伴鼻息肉和不伴鼻息肉的黏膜上皮修复机制中的作用[J]. 临床耳鼻咽喉头颈外科杂志, 2019, 33(1): 9-13. https://www.cnki.com.cn/Article/CJFDTOTAL-LCEH201901003.htm WANG T, ZANG H R, LI Y C, et al. The role of Smad signaling pathway in the repair of mucosal epithelium in chronic sinusitis with nasal polyps and without nasal polyps[J]. Journal of Clinical Otorhinolaryngology Head and Neck Surgery, 2019, 33(1): 9-13. https://www.cnki.com.cn/Article/CJFDTOTAL-LCEH201901003.htm
[30]	KIM S J, PARK J H, LEE S A, et al. All-trans retinoic acid regulates TGF-β1-induced extracellular matrix production via p38, JNK, and NF-κB-signaling pathways in nasal polyp-derived fibroblasts[J]. Int Forum Allergy Rhinol, 2020, 10(5): 636-645. doi: 10.1002/alr.22525
[31]	YAN B, WANG Y, LI Y, et al. Inhibition of arachidonate 15-lipoxygenase reduces the epithelial-mesenchymal transition in eosinophilic chronic rhinosinusitis with nasal polyps[J]. Int Forum Allergy Rhinol, 2019, 9(3): 270-280. doi: 10.1002/alr.22243
[32]	沙敏, 李勇, 李静. HGF与TGF-β1的平衡在慢性鼻窦炎组织重塑中的作用[J]. 中华全科医学, 2017, 15(4): 663-666. doi: 10.16766/j.cnki.issn.1674-4152.2017.04.037 SHA M, LI Y, LI J. The balance of HGF and TGF-β1 in the remodeling of chronic rhinosinusitis[J]. Chinese Journal of General Practice, 2017, 15(4): 663-666. doi: 10.16766/j.cnki.issn.1674-4152.2017.04.037
[33]	LAI Y T, ZHANG P Y, WANG H, et al. Serum and glucocorticoid-regulated kinase 1 regulates transforming growth factor β1-connective tissue growth factor pathway in chronic rhinosinusitis[J]. Clin Immunol, 2022, 234: 108895. DOI: 10.1016/j.clim,2021.108895.
[34]	YANG H W, KIM H J, PARK J H, et al. Apigenin alleviates TGF-β1-induced nasal mucosa remodeling by inhibiting MAPK/NF-kB signaling pathways in chronic rhinosinusitis[J]. PLoS One, 2018, 13(8): e0201595. DOI: 10.1371/journal.pone.0201595.
[35]	LYGEROS S, DANIELIDES G, GRAFANAKI K, et al. Matrix metalloproteinases and chronic rhinosinusitis with nasal polyposis. Unravelling a puzzle through a systematic review[J]. Rhinology, 2021, 59(3): 245-257.
[36]	PARK J H, SHIN J M, YANG H W, et al. Cigarette smoke extract stimulates MMP-2 production in nasal fibroblasts via ROS/PI3K, Akt, and NF-κB signaling pathways[J]. Antioxidants (Basel), 2020, 9(8): 739. doi: 10.3390/antiox9080739
[37]	DU K, WANG M, ZHANG N, et al. Involvement of the extracellular matrix proteins periostin and tenascin C in nasal polyp remodeling by regulating the expression of MMPs[J]. Clin Transl Allergy, 2021, 11(7): e12059. DOI: 10.1002/clt2.12059.
[38]	LYGEROS S, DANIELIDES G, KYRIAKOPOULOS G C, et al. Evaluation of MMP-12 expression in chronic rhinosinusitis with nasal polyposis[J]. Rhinology, 2022, 60(1): 39-46.
[39]	SHI L L, MA J, DENG Y K, et al. Cold-inducible RNA-binding protein contributes to tissue remodeling in chronic rhinosinusitis with nasal polyps[J]. Allergy, 2021, 76(2): 497-509. doi: 10.1111/all.14287
[40]	LEES K A, ORLANDI R R, OAKLEY G, ALT J A. The Role of macrolides and doxycycline in chronic rhinosinusitis[J]. Immunol Allergy Clin North Am, 2020, 40(2): 303-315. doi: 10.1016/j.iac.2019.12.005
[41]	ANTONIO M A, MARSON F A L, TORO M D C, et al. Topical tretinoin in chronic rhinosinusitis with nasal polyps: A randomized clinical trial[J]. Int Forum Allergy Rhinol, 2021, 11(8): 1187-1196. doi: 10.1002/alr.22778
[42]	KIM H J, PARK J H, SHIN J M, et al. Author Correction: TGF-β1-induced HSP47 regulates extracellular matrix accumulation via Smad2/3 signaling pathways in nasal fibroblasts[J]. Sci Rep, 2020, 10(1): 9585. doi: 10.1038/s41598-020-66547-z
[43]	SHIEH J M, TSAI Y J, CHI J C, et al. TGFβ mediates collagen production in human CRSsNP nasal mucosa-derived fibroblasts through Smad2/3-dependent pathway and CTGF induction and secretion[J]. J Cell Physiol, 2019, 234(7): 10489-10499. doi: 10.1002/jcp.27718
[44]	韩佳琦, 苑国庆, 朱宇彤, 等. 慢性鼻窦炎伴鼻息肉患者血清25-(OH)D₃和组织中TGF-β1水平及临床意义[J]. 山东大学耳鼻喉眼学报, 2021, 35(5): 23-27. https://www.cnki.com.cn/Article/CJFDTOTAL-SDYU202105004.htm HAN J Q, YUAN G Q, ZHU Y T, et al. Serum 25-(OH) D3 and tissue TGF-β1 levels in patients with chronic rhino sinusitis with nasal polyps and their clinical significance[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2021, 35(5): 23-27. https://www.cnki.com.cn/Article/CJFDTOTAL-SDYU202105004.htm