DNA甲基化与口腔疾病的研究进展
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摘要
DNA甲基化现在被广泛认为是维持免疫细胞功能的关键。异常的DNA甲基化水平与常见的口腔疾病相关。环境因素和遗传多态性导致甲基化异常,影响某些免疫相关基因的表达,成为研究口腔疾病机制的热点。本文综述了在慢性牙周炎、口腔癌、口腔扁平苔藓等常见口腔疾病发展过程中异常甲基化的重要性,以及DNA甲基化与复发性阿弗他溃疡关系的研究展望,目的是更清楚地了解口腔疾病的发病机制,从而为治疗复杂性口腔疾病提供新的思路。
DNA methylation is the key to maintaining the function of immune cells. Recent studies have shown that abnormal DNA methylation levels are significantly associated with common oral diseases. Environmental factors and genetic polymorphism lead to abnormal methylation and affect the expression of some immune-related genes. This paper reviewed the importance of abnormal DNA methylation in the development of common oral diseases(e.g. chronic periodontitis, oral cancer and oral lichen planus) and the relationship between DNA methylation and recurrent aphthous ulcer. This paper provides improved understanding of the pathogenesis of oral diseases and new insights into the treatment of oral diseases.
DNA methylation is the key to maintaining the function of immune cells. Recent studies have shown that abnormal DNA methylation levels are significantly associated with common oral diseases. Environmental factors and genetic polymorphism lead to abnormal methylation and affect the expression of some immune-related genes. This paper reviewed the importance of abnormal DNA methylation in the development of common oral diseases(e.g. chronic periodontitis, oral cancer and oral lichen planus) and the relationship between DNA methylation and recurrent aphthous ulcer. This paper provides improved understanding of the pathogenesis of oral diseases and new insights into the treatment of oral diseases.
引文
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[27]Liu H,Liu XW,Dong G,et al.P16 methylation as an early predictor for cancer development from oral epithelial dysplasia:a double-blind multicentre prospective study[J].EBioMedicine,2015,2(5):432-437.
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[29]Fonseca-Silva T,Oliveira MV,Fraga CA,et al.DNMT-3B(C46359T)polymorphisms and immunoexpression of DNMT3b and DNMT1 proteins in oral lichen planus[J].Pathobiology,2012,79(1):18-23.
[30]Cruz AF,de Resende RG,de Lacerda JCT,et al.DNA methylation patterns of genes related to immune response in the different clinical forms of oral lichen planus[J].J Oral Pathol Med,2018,47(1):91-95.
[31]陈谦明,周曾同.口腔黏膜病学[M].3版.北京:人民卫生出版社,2008.Chen QM,Zhou ZT.Oral mucosa diseases[M].3rd ed.Beijing:People’s Health Publishing House,2008.
[32]管翠强,武云霞,郭洪波.复发性口腔溃疡血清叶酸和维生素B12的临床观察[J].山西医科大学学报,2014,45(5):395-397.Guan CQ,Wu YX,Guo HB.Clinical observation on serum folic acid and vitamin B12 in patients with recurrent oral ulcer[J].J Shanxi Med Univ,2014,45(5):395-397.
[33]刘好好,许子悦,谢春雨,等.复发性口腔溃疡与T细胞免疫研究进展[J].现代免疫学,2016,36(1):72-75.Liu HH,Xu ZY,Xie CY,et al.Recurrent oral ulcer and T cell immunity[J].Curr Immunol,2016,36(1):72-75.
[34]郭洪波,管翠强.加味导赤散对复发性口腔溃疡患者Th1/Th2平衡的调节作用[J].中国药物与临床,2015,15(12):1745-1747.Guo HB,Guan CQ.Regulatory effect of Jiawei Daochi Powder on Th1/Th2 balance in patients with recurrent oral ulcer[J].Chin Remed Clin,2015,15(12):1745-1747.
[35]杜芹,田鲲,廖楚航.复发性阿弗他溃疡Th1/Th2细胞因子的检测[J].成都医学院学报,2013,8(6):657-660.Du Q,Tian K,Liao CH.Expression of Thl/Th2-related cytokines in recurrent Aphthous ulcers[J].JChengdu Med Coll,2013,8(6):657-660.
[36]Lewkowicz N,Kur B,Kurnatowska A,et al.Expression of Th1/Th2/Th3/Th17-related genes in recurrent aphthous ulcers[J].Arch Immunol Ther Exp(Warsz),2011,59(5):399-406.
[37]Bird JJ,Brown DR,Mullen AC,et al.Helper T cell differentiation is controlled by the cell cycle[J].Immunity,1998,9(2):229-237.
[38]Brand S,Kesper DA,Teich R,et al.DNA methylation of TH1/TH2 cytokine genes affects sensitization and progress of experimental asthma[J].J Allergy Clin Immunol,2012,129(6):1602-1610.
[2]Quintero-Ronderos P,Montoya-Ortiz G.Epigenetics and autoimmune diseases[J].Autoimmune Dis,2012,2012:593720.
[3]Kim H,Wang X,Jin P.Developing DNA methylation-based diagnostic biomarkers[J].J Genet Genomics,2018,45(2):87-97.
[4]Rodriguez RM,Lopez-Larrea C,Suarez-Alvarez B.Epigenetic dynamics during CD4+T cells lineage commitment[J].Int J Biochem Cell Biol,2015,67:75-85.
[5]Zhang S,Barros SP,Moretti AJ,et al.Epigenetic regulation of TNFA expression in periodontal disease[J].J Periodontol,2013,84(11):1606-1616.
[6]Dor Y,Cedar H.Principles of DNA methylation and their implications for biology and medicine[J].Lancet,2018,392(10149):777-786.
[7]Sun B,Hu L,Luo ZY,et al.DNA methylation perspectives in the pathogenesis of autoimmune diseases[J].Clin Immunol,2016,164:21-27.
[8]Jin Z,Liu Y.DNA methylation in human diseases[J].Genes Dis,2018,5(1):1-8.
[9]Deaton AM,Bird A.CpG islands and the regulation of transcription[J].Genes Dev,2011,25(10):1010-1022.
[10]Williams K,Christensen J,Helin K.DNA methylation:TET proteins-guardians of CpG islands[J].EMBORep,2011,13(1):28-35.
[11]Tahara T,Shibata T,Arisawa T,et al.CpG island promoter methylation(CIHM)status of tumor suppressor genes correlates with morphological appearances of gastric cancer[J].Anticancer Res,2010,30(1):239-244.
[12]史玉杰,李庆贺,刘晓辉.DNA甲基化与基因表达调控研究进展[J].中国生物工程杂志,2013,33(7):90-96.Shi YJ,Li QH,Liu XH.Progress in studies of DNAmethylation and gene expression regulation[J].Chin Biotechnol,2013,33(7):90-96.
[13]Singh A,Gill G,Jakhu H.Epigenetics and its implications for oral health[J].J Oral Biosci,2018,60(2):41-48.
[14]Abiko Y,Uehara O,Fukumoto S,et al.Epigenetics of oral infection and inflammatory diseases-DNAmethylation changes in infections and inflammation diseases[J].J Oral Biosci,2014,56(4):105-109.
[15]唐秋玲,李格格,潘佳慧,等.细胞焦亡与牙龈卟啉单胞菌的关系及其在牙周病发生发展中的作用机制[J].国际口腔医学杂志,2017,44(6):660-663.Tang QL,Li GG,Pan JH,et al.Mechanism of pyroptosis and Porphyromonas gingivalis in periodontitis development process[J].Int J Stomatol,2017,44(6):660-663.
[16]Stefani FA,Viana MB,Dupim AC,et al.Expression,polymorphism and methylation pattern of interleukin-6in periodontal tissues[J].Immunobiology,2013,218(7):1012-1017.
[17]Ahmadi M,Gharibi T,Dolati S,et al.Epigenetic modifications and epigenetic based medication implemen tations of autoimmune diseases[J].Biomed Pharmacother,2017,87:596-608.
[18]Viana MB,Cardoso FP,Diniz MG,et al.Methylation pattern of IFN-γand IL-10 genes in periodontal tissues[J].Immunobiology,2011,216(8):936-941.
[19]Zhang S,Crivello A,Offenbacher S,et al.Interferon-γpromoter hypomethylation and increased expression in chronic periodontitis[J].J Clin Periodontol,2010,37(11):953-961.
[20]Nikitakis NG,Rassidakis GZ,Tasoulas J,et al.Altera tions in the expression of DNA damage responserelated molecules in potentially preneoplastic oral epithelial lesions[J].Oral Surg Oral Med Oral Pathol Oral Radiol,2018,125(6):637-649.
[21]Sankaranarayanan R,Sauvaget C,Ramadas K,et al.Clinical trials of cancer screening in the developing world and their impact on cancer healthcare[J].Ann Oncol,2011,22(Suppl 7):vii20-vii28.
[22]Towle R,Truong D,Hogg K,et al.Global analysis of DNA methylation changes during progression of oral cancer[J].Oral Oncol,2013,49(11):1033-1042.
[23]Arantes LM,de Carvalho AC,Melendez ME,et al.Validation of methylation markers for diagnosis of oral cavity cancer[J].Eur J Cancer,2015,51(5):632-641.
[24]Breitling LP,Yang R,Korn B,et al.Tobacco-smoking-related differential DNA methylation:27K discovery and replication[J].Am J Hum Genet,2011,88(4):450-457.
[25]Dang J,Bian YQ,Sun JY,et al.MicroRNA-137 promoter methylation in oral lichen planus and oral squamous cell carcinoma[J].J Oral Pathol Med,2013,42(4):315-321.
[26]Cao J,Zhou J,Gao Y,et al.Methylation of p16 CpGisland associated with malignant progression of oral epithelial dysplasia:a prospective cohort study[J].Clin Cancer Res,2009,15(16):5178-5183.
[27]Liu H,Liu XW,Dong G,et al.P16 methylation as an early predictor for cancer development from oral epithelial dysplasia:a double-blind multicentre prospective study[J].EBioMedicine,2015,2(5):432-437.
[28]刘雅菁,王文梅.口腔扁平苔藓中T淋巴细胞亚群的研究进展[J].国际口腔医学杂志,2011,38(4):433-435.Liu YJ,Wang WM.Research progress on T lymphocyte subsets of oral lichen planus[J].Int J Stomatol,2011,38(4):433-435.
[29]Fonseca-Silva T,Oliveira MV,Fraga CA,et al.DNMT-3B(C46359T)polymorphisms and immunoexpression of DNMT3b and DNMT1 proteins in oral lichen planus[J].Pathobiology,2012,79(1):18-23.
[30]Cruz AF,de Resende RG,de Lacerda JCT,et al.DNA methylation patterns of genes related to immune response in the different clinical forms of oral lichen planus[J].J Oral Pathol Med,2018,47(1):91-95.
[31]陈谦明,周曾同.口腔黏膜病学[M].3版.北京:人民卫生出版社,2008.Chen QM,Zhou ZT.Oral mucosa diseases[M].3rd ed.Beijing:People’s Health Publishing House,2008.
[32]管翠强,武云霞,郭洪波.复发性口腔溃疡血清叶酸和维生素B12的临床观察[J].山西医科大学学报,2014,45(5):395-397.Guan CQ,Wu YX,Guo HB.Clinical observation on serum folic acid and vitamin B12 in patients with recurrent oral ulcer[J].J Shanxi Med Univ,2014,45(5):395-397.
[33]刘好好,许子悦,谢春雨,等.复发性口腔溃疡与T细胞免疫研究进展[J].现代免疫学,2016,36(1):72-75.Liu HH,Xu ZY,Xie CY,et al.Recurrent oral ulcer and T cell immunity[J].Curr Immunol,2016,36(1):72-75.
[34]郭洪波,管翠强.加味导赤散对复发性口腔溃疡患者Th1/Th2平衡的调节作用[J].中国药物与临床,2015,15(12):1745-1747.Guo HB,Guan CQ.Regulatory effect of Jiawei Daochi Powder on Th1/Th2 balance in patients with recurrent oral ulcer[J].Chin Remed Clin,2015,15(12):1745-1747.
[35]杜芹,田鲲,廖楚航.复发性阿弗他溃疡Th1/Th2细胞因子的检测[J].成都医学院学报,2013,8(6):657-660.Du Q,Tian K,Liao CH.Expression of Thl/Th2-related cytokines in recurrent Aphthous ulcers[J].JChengdu Med Coll,2013,8(6):657-660.
[36]Lewkowicz N,Kur B,Kurnatowska A,et al.Expression of Th1/Th2/Th3/Th17-related genes in recurrent aphthous ulcers[J].Arch Immunol Ther Exp(Warsz),2011,59(5):399-406.
[37]Bird JJ,Brown DR,Mullen AC,et al.Helper T cell differentiation is controlled by the cell cycle[J].Immunity,1998,9(2):229-237.
[38]Brand S,Kesper DA,Teich R,et al.DNA methylation of TH1/TH2 cytokine genes affects sensitization and progress of experimental asthma[J].J Allergy Clin Immunol,2012,129(6):1602-1610.
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