组蛋白乙酰化修饰在哮喘发病机制中的研究进展

doi:10.12114/j.issn.1007-9572.2021.01.015

摘要/Abstract

摘要： 哮喘主要以气道炎症、气道重塑和气道高反应性为特征。组蛋白乙酰化是最常见的表观遗传修饰之一，主要指组蛋白乙酰转移酶和组蛋白去乙酰化酶的调节，调节失衡会导致病理变化。该文回顾论述了近5年来组蛋白乙酰化修饰在哮喘发病机制中的研究，揭示系统和深入研究的发展方向，旨在为临床治疗提供依据。

关键词: 哮喘, 组蛋白乙酰化, 组蛋白酰基转移酶, 组蛋白去乙酰化酶, 综述

Abstract:

Asthma is primarily marked by airway hyperresponsiveness, inflammation, and remodeling. Histone acetylation is one of the most common epigenetic modifications that regulates histone acetyltransferase and histone deacetylase, and imbalanced regulation may lead to pathological changes. We reviewed the advances in histone acetylation in the pathogenesis of asthma in recent five years, revealing the direction of systematic and in-depth research, in order to provide evidence for clinical treatment.

Key words: Asthma, Histone acetylation, Histone acetyltransferase, Histone deacetylase, Review

中图分类号:

R562.25

陈绍鹏,曾敏娟,赖天文. 组蛋白乙酰化修饰在哮喘发病机制中的研究进展[J]. 中国全科医学, 2022, 25(05): 631-635. DOI: 10.12114/j.issn.1007-9572.2021.01.015.

CHEN Shaopeng, ZENG Minjuan, LAI Tianwen.

Latest Research Development in Histone Acetylation in the Pathogenesis of Asthma [J]. Chinese General Practice, 2022, 25(05): 631-635.

图/表 1

参考文献 41

[1]	CHUNG S, LEE Y G, KARPURAPU M，et al. Depletion of microRNA-451 in response to allergen exposure accentuates asthmatic inflammation by regulating Sirtuin2[J]. Am J Physiol Lung Cell Mol Physiol，2020，318(5):L921-930. DOI：10.1152/ajplung.00457.2019.
[2]	XIA M L, XU H, DAI W，et al. The role of HDAC2 in cigarette smoke-induced airway inflammation in a murine model of asthma and the effect of intervention with roxithromycin[J]. J Asthma，2018，55(4):337-344. DOI：10.1080/02770903.2017.1337788.
[3]	ZHOU J, GENG F H, XU J M，et al. PM2.5 exposure and cold stress exacerbates asthma in mice by increasing histone acetylation in IL-4 gene promoter in CD4+ T cells[J]. Toxicol Lett，2019，316:147-153. DOI：10.1016/j.toxlet.2019.09.011.
[4]	MA L Y, BIAN X, LIN W C. The dual HDAC-PI3K inhibitor CUDC-907 displays single-agent activity and synergizes with PARP inhibitor olaparib in small cell lung cancer[J]. J Exp Clin Cancer Res，2020，39(1):219. DOI：10.1186/s13046-020-01728-2.
[5]	CHENG Q, SHANG Y X, HUANG W J，et al. p300 mediates the histone acetylation of ORMDL3 to affect airway inflammation and remodeling in asthma[J]. Int Immunopharmacol，2019，76:105885. DOI：10.1016/j.intimp.2019.105885.
[6]	TANG L L, CHEN Q G, MENG Z Y，et al. Suppression of sirtuin-1 increases IL-6 expression by activation of the Akt pathway during allergic asthma[J]. Cell Physiol Biochem，2017，43(5):1950-1960. DOI：10.1159/000484119.
[7]	STYLIANOU E. Epigenetics of chronic inflammatory diseases[J].J Inflamm Res，2019，12:1-14. DOI：10.2147/JIR.S129027.
[8]	HE J, QIN M, CHEN Y Y，et al. Epigenetic regulation of matrix metalloproteinases in inflammatory diseases：a narrative review[J]. Cell Biosci，2020，10:86. DOI：10.1186/s13578-020-00451-x.
[9]	KOOPMANS T, EILERS R, MENZEN M，et al. Β-catenin directs nuclear factor-κB p65 output via CREB-binding protein/p300 in human airway smooth muscle[J]. Front Immunol，2017，8:1086. DOI：10.3389/fimmu.2017.01086.
[10]	HUANG Z W, LIEN G S, LIN C H，et al. p300 and C/EBPβ-regulated IKKβ expression are involved in thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells[J]. Pharmacol Res，2017，121:33-41. DOI：10.1016/j.phrs.2017.04.020.
[11]	CUI Z L, GU W, DING T，et al. Histone modifications of Notch1 promoter affect lung CD4+T cell differentiation in asthmatic rats[J]. Int J Immunopathol Pharmacol，2013，26(2):371-381. DOI：10.1177/039463201302600210.
[12]	XIAO X, FAN Y H, LI J H，et al. Guidance of super-enhancers in regulation of IL-9 induction and airway inflammation[J]. J Exp Med，2018，215(2):559-574. DOI：10.1084/jem.20170928.
[13]	MALLESKE D T, HAYES D Jr, LALLIER S W，et al. Regulation of human airway epithelial tissue stem cell differentiation by β-catenin，P300，and CBP[J]. Stem Cells，2018，36(12):1905-1916. DOI：10.1002/stem.2906.
[14]	SU X M, REN Y, LI M L，et al. Performance evaluation of histone deacetylases in lungs of mice exposed to ovalbumin aerosols[J]. J Physiol Pharmacol，2018，69(2). DOI：10.26402/jpp.2018.2.12.
[15]	LI M L, SU X M, REN Y，et al. HDAC8 inhibitor attenuates airway responses to antigen stimulus through synchronously suppressing galectin-3 expression and reducing macrophage-2 polarization[J]. Respir Res，2020，21(1):62. DOI：10.1186/s12931-020-1322-5.
[16]	HIRAI K, SHIRAI T, RACHI Y，et al. Impact of gene expression associated with glucocorticoid-induced transcript 1 （GLCCI1） on severe asthma and future exacerbation[J]. Biol Pharm Bull，2019，42(10):1746-1752. DOI：10.1248/bpb.b19-00476.
[17]	LAI T W, WU M D, ZHANG C，et al. HDAC2 attenuates airway inflammation by suppressing IL-17A production in HDM-challenged mice[J]. Am J Physiol Lung Cell Mol Physiol，2019，316(1):L269-279. DOI：10.1152/ajplung.00143.2018.
[18]	SAKURAI H, MORISHIMA Y, ISHII Y，et al. Sulforaphane ameliorates steroid insensitivity through an Nrf2-dependent pathway in cigarette smoke-exposed asthmatic mice[J]. Free Radic Biol Med，2018，129:473-485. DOI：10.1016/j.freeradbiomed.2018.10.400.
[19]	BARNES P J. Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease[J]. J Allergy Clin Immunol，2013，131(3):636-645. DOI：10.1016/j.jaci.2012.12.1564.
[20]	FERRARO M, GJOMARKAJ M, SIENA L，et al. Formoterol and fluticasone propionate combination improves histone deacetylation and anti-inflammatory activities in bronchial epithelial cells exposed to cigarette smoke[J]. Biochim Biophys Acta Mol Basis Dis，2017，1863(7):1718-1727. DOI：10.1016/j.bbadis.2017.05.003.
[21]	ZHANG H P, WANG L, FU J J，et al. Association between histone hyperacetylation status in memory T lymphocytes and allergen-induced eosinophilic airway inflammation[J]. Respirology，2016，21(5):850-857. DOI：10.1111/resp.12774.
[22]	PAN Y L, LIU L, LI S J，et al. Activation of AMPK inhibits TGF-β1-induced airway smooth muscle cells proliferation and its potential mechanisms[J]. Sci Rep，2018，8(1):3624. DOI：10.1038/s41598-018-21812-0.
[23]	LU Y, LI Z J, XIE B Q，et al. Hsa-miR-20a-5p attenuates allergic inflammation in HMC-1 cells by targeting HDAC4[J]. Mol Immunol，2019，107:84-90. DOI：10.1016/j.molimm.2019.01.010.
[24]	HOU X X, WAN H Y, AI X Y，et al. Histone deacetylase inhibitor regulates the balance of Th17/Treg in allergic asthma[J]. Clin Respir J，2016，10(3):371-379. DOI：10.1111/crj.12227.
[25]	MA K, LU N, ZOU F，et al. Sirtuins as novel targets in the pathogenesis of airway inflammation in bronchial asthma[J]. Eur J Pharmacol，2019，865:172670. DOI：10.1016/j.ejphar.2019.172670.
[26]	LEE Y G, READER B F, HERMAN D，et al. Sirtuin 2 enhances allergic asthmatic inflammation[J]. JCI Insight，2019，4(4):124710. DOI：10.1172/jci.insight.124710.
[27]	FANG P, XUE Y, ZHANG Y H，et al. SIRT7 regulates the TGF-β1-induced proliferation and migration of mouse airway smooth muscle cells by modulating the expression of TGF-β receptor I[J]. Biomedecine Pharmacother，2018，104:781-787. DOI：10.1016/j.biopha.2018.05.060.
[28]	JANG H Y, GU S N, LEE S M，et al. Overexpression of sirtuin 6 suppresses allergic airway inflammation through deacetylation of GATA3[J]. J Allergy Clin Immunol，2016，138(5):1452-1455.e13. DOI：10.1016/j.jaci.2016.05.019.
[29]	LIU F, SHANG Y X. Sirtuin 6 attenuates epithelial-mesenchymal transition by suppressing the TGF-β1/Smad3 pathway and c-Jun in asthma models[J]. Int Immunopharmacol，2020，82:106333. DOI：10.1016/j.intimp.2020.106333.
[30]	ZHANG Y Z, WU Q J, YANG X，et al. Effects of SIRT1/Akt pathway on chronic inflammatory response and lung function in patients with asthma[J]. Eur Rev Med Pharmacol Sci，2019，23(11):4948-4953. DOI：10.26355/eurrev_201906_18085.
[31]	ZHANG H, SUN Y C, RONG W，et al. miR-221 participates in the airway epithelial cells injury in asthma via targeting SIRT1[J]. Exp Lung Res，2018，44(6):272-279. DOI：10.1080/01902148.2018.1533051.
[32]	TIEN C P, CHEN C H, LIN W Y，et al. Ambient particulate matter attenuates Sirtuin1 and augments SREBP1-PIR axis to induce human pulmonary fibroblast inflammation：molecular mechanism of microenvironment associated with COPD[J]. Aging （Albany NY），2019，11(13):4654-4671. DOI：10.18632/aging.102077.
[33]	TOKI S, GOLENIEWSKA K, REISS S，et al. The histone deacetylase inhibitor trichostatin A suppresses murine innate allergic inflammation by blocking group 2 innate lymphoid cell （ILC2） activation[J]. Thorax，2016，71(7):633-645. DOI：10.1136/thoraxjnl-2015-207728.
[34]	REN Y, SU X M, KONG L F，et al. Therapeutic effects of histone deacetylase inhibitors in a murine asthma model[J]. Inflamm Res，2016，65(12):995-1008. DOI：10.1007/s00011-016-0984-4.
[35]	THIO C L, CHI P Y, LAI A C，et al. Regulation of type 2 innate lymphoid cell-dependent airway hyperreactivity by butyrate[J]. J Allergy Clin Immunol，2018，142(6):1867-1883.e12. DOI：10.1016/j.jaci.2018.02.032.
[36]	CAO F Y, DE WEERD S, CHEN D，et al. Induced protein degradation of histone deacetylases 3 （HDAC3） by proteolysis targeting chimera （PROTAC）[J]. Eur J Med Chem，2020，208:112800. DOI：10.1016/j.ejmech.2020.112800.
[37]	KIM R Y, HORVAT J C, PINKERTON J W，et al. MicroRNA-21 drives severe，steroid-insensitive experimental asthma by amplifying phosphoinositide 3-kinase-mediated suppression of histone deacetylase 2[J]. J Allergy Clin Immunol，2017，139(2):519-532. DOI：10.1016/j.jaci.2016.04.038.
[38]	BI J, MIN Z H, YUAN H L，et al. PI3K inhibitor treatment ameliorates the glucocorticoid insensitivity of PBMCs in severe asthma[J]. Clin Transl Med，2020，9(1):22. DOI：10.1186/s40169-020-0262-5.
[39]	ITO K, LIM S, CARAMORI G，et al. A molecular mechanism of action of theophylline：Induction of histone deacetylase activity to decrease inflammatory gene expression[J]. Proc Natl Acad Sci USA，2002，99(13):8921-8926. DOI：10.1073/pnas.132556899.
[40]	LIAO W P, TAN W S, WONG W S. Andrographolide restores steroid sensitivity to block lipopolysaccharide/IFN-γ-induced IL-27 and airway hyperresponsiveness in mice[J]. J Immunol，2016，196(11):4706-4712. DOI：10.4049/jimmunol.1502114.
[41]	BRITT R D Jr, THOMPSON M A, FREEMAN M R，et al. Vitamin D reduces inflammation-induced contractility and remodeling of asthmatic human airway smooth muscle[J]. Ann Am Thorac Soc，2016，13():S97-98. DOI：10.1513/AnnalsATS.201508-540MG.