Epigenetic Modifications and Therapy in Chronic Obstructive Pulmonary Disease (COPD): An Update Review

References

• Vestbo J, Hurd SS, Rodriguez‐Roisin R. The 2011 revision of the global strategy for the diagnosis, management and prevention of COPD (GOLD)-why and what? Clin Respir J. 2012;6(4):208–214. doi:10.1111/crj.12002.
   PubMed Web of Science ®Google Scholar
• Shapiro SD, Ingenito EP. The pathogenesis of chronic obstructive pulmonary disease: advances in the past 100 years. Am J Respir Cell Mol Biol. 2005;32(5):367–372. doi:10.1165/rcmb.F296.
   PubMed Web of Science ®Google Scholar
• Marwick JA, Kirkham PA, Stevenson CS, et al. Cigarette smoke alters chromatin remodeling and induces proinflammatory genes in rat lungs. Am J Respir Cell Mol Biol. 2004;31(6):633–642. doi:10.1165/rcmb.2004-0006OC.
   PubMed Web of Science ®Google Scholar
• Pandey R, Singh M, Singhal U, et al. Oxidative/nitrosative stress and the pathobiology of chronic obstructive pulmonary disease. J Clin Diagn Res. 2013;7(3):580–588. doi:10.7860/JCDR/2013/4360.2832.
   PubMedGoogle Scholar
• Rahman I. Oxidative stress in pathogenesis of chronic obstructive pulmonary disease: cellular and molecular mechanisms. Cell Biochem Biophys. 2005;43(1):167–188. doi:10.1385/CBB:43:1:167.
   PubMed Web of Science ®Google Scholar
• Rahman I, Adcock I. Oxidative stress and redox regulation of lung inflammation in COPD. Eur Respir J. 2006;28(1):219–242. doi:10.1183/09031936.06.00053805.
   PubMed Web of Science ®Google Scholar
• Adcock IM, Ford P, Ito K, et al. Epigenetics and airways disease. Respir Res. 2006;7(1):21. doi:10.1186/1465-9921-7-21.
   PubMedGoogle Scholar
• Gosden RG, Feinberg AP. Genetics and epigenetics—nature’s pen-and-pencil set. N Engl J Med. 2007;356(7):731–733. doi:10.1056/NEJMe068284.
   PubMed Web of Science ®Google Scholar
• Li B, Carey M, Workman JL. The role of chromatin during transcription. Cell. 2007;128(4):707–719. doi:10.1016/j.cell.2007.01.015.
   PubMed Web of Science ®Google Scholar
• Yang IV, Schwartz DA. Epigenetic control of gene expression in the lung. Am J Respir Crit Care Med. 2011;183(10):1295–1301. doi:10.1164/rccm.201010-1579PP.
   PubMed Web of Science ®Google Scholar
• Aslani S, Jafari N, Javan MR, et al. Epigenetic modifications and therapy in multiple sclerosis. Neuromolecular Med. 2017;19(1):11–23. doi:10.1007/s12017-016-8422-x.
   PubMed Web of Science ®Google Scholar
• Wu D-D, Song J, Bartel S, et al. The potential for targeted rewriting of epigenetic marks in COPD as a new therapeutic approach. Pharmacol Ther. 2018;182:1–14. doi:10.1016/j.pharmthera.2017.08.007.
   PubMed Web of Science ®Google Scholar
• Kamrani A, Alipourfard I, Ahmadi‐Khiavi H, et al. The role of epigenetic changes in preeclampsia. Biofactors. 2019;45(5):712–724. doi:10.1002/biof.1542.
   PubMed Web of Science ®Google Scholar
• Comer BS, Ba M, Singer CA, et al. Epigenetic targets for novel therapies of lung diseases. Pharmacol Ther. 2015;147:91–110. doi:10.1016/j.pharmthera.2014.11.006.
   PubMed Web of Science ®Google Scholar
• Chendrimada TP, Gregory RI, Kumaraswamy E, et al. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature. 2005;436(7051):740–744. doi:10.1038/nature03868.
   PubMed Web of Science ®Google Scholar
• Lytle JR, Yario TA, Steitz JA. Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5' UTR as in the 3' UTR. Proc Natl Acad Sci Usa. 2007;104(23):9667–9672. doi:10.1073/pnas.0703820104.
   PubMed Web of Science ®Google Scholar
• Ahmadi M, Gharibi T, Dolati S, et al. Epigenetic modifications and epigenetic based medication implementations of autoimmune diseases. Biomed Pharmacother. 2017;87:596–608. doi:10.1016/j.biopha.2016.12.072.
   PubMed Web of Science ®Google Scholar
• Zong D, Ouyang R, Chen P. Epigenetic mechanisms in chronic obstructive pulmonary disease. Eur Rev Med Pharmacol Sci. 2015;19(5):844–856.
   PubMed Web of Science ®Google Scholar
• Rajendrasozhan S, Yao H, Rahman I. Current perspectives on role of chromatin modifications and deacetylases in lung inflammation in COPD. COPD. 2009;6(4):291–297. doi:10.1080/15412550903049132.
   PubMedGoogle Scholar
• Wang Z, Schones DE, Zhao K. Characterization of human epigenomes. Curr Opin Genet Dev. 2009;19(2):127–134. doi:10.1016/j.gde.2009.02.001.
   PubMed Web of Science ®Google Scholar
• Peng H, Guo T, Chen Z, et al. Hypermethylation of mitochondrial transcription factor A induced by cigarette smoke is associated with chronic obstructive pulmonary disease. Exp Lung Res. 2019;45(3–4):101–111. doi:10.1080/01902148.2018.1556748.
   PubMed Web of Science ®Google Scholar
• Lee MK, Xu C-J, Carnes MU, et al. Genome-wide DNA methylation and long-term ambient air pollution exposure in Korean adults. Clin Epigenet. 2019;11(1):37. doi:10.1186/s13148-019-0635-z.
   PubMed Web of Science ®Google Scholar
• Tzortzaki EG, Papi A, Neofytou E, et al. Immune and genetic mechanisms in COPD: possible targets for therapeutic interventions. Curr Drug Targets. 2013;14(2):141–148. doi:10.2174/1389450111314020002.
   PubMed Web of Science ®Google Scholar
• Qiu W, Baccarelli A, Carey VJ, et al. Variable DNA methylation is associated with chronic obstructive pulmonary disease and lung function. Am J Respir Crit Care Med. 2012;185(4):373–381. doi:10.1164/rccm.201108-1382OC.
   PubMed Web of Science ®Google Scholar
• Bruscia EM, Bonfield TL. Cystic fibrosis lung immunity: the role of the macrophage. J Innate Immun. 2016;8(6):550–563. doi:10.1159/000446825.
   PubMed Web of Science ®Google Scholar
• West J. Regional differences in gas exchange in the lung of erect man. J Appl Physiol. 1962;17(6):893–898. doi:10.1152/jappl.1962.17.6.893.
   PubMed Web of Science ®Google Scholar
• Armstrong DA, Chen Y, Dessaint JA, et al. DNA Methylation Changes in Regional Lung Macrophages Are Associated with Metabolic Differences. IH. 2019;3(7):274–281. doi:10.4049/immunohorizons.1900042.
   Google Scholar
• Nakahira K, Hisata S, Choi AM. The roles of mitochondrial damage-associated molecular patterns in diseases. Antioxid Redox Signal. 2015;23(17):1329–1350. doi:10.1089/ars.2015.6407.
   PubMed Web of Science ®Google Scholar
• Remels A, Schrauwen P, Broekhuizen R, et al. Peroxisome proliferator-activated receptor expression is reduced in skeletal muscle in COPD. Eur Respir J. 2007;30(2):245–252. doi:10.1183/09031936.00144106.
   PubMed Web of Science ®Google Scholar
• Campbell CT, Kolesar JE, Kaufman BA. Mitochondrial transcription factor A regulates mitochondrial transcription initiation, DNA packaging, and genome copy number. Biochim Biophys Acta. 2012;1819(9-10):921–929. doi:10.1016/j.bbagrm.2012.03.002.
   PubMed Web of Science ®Google Scholar
• Patel V, Kantipudi N, Jones G, et al. Air pollution and cardiovascular disease: a review. Crit Rev Biomed Eng. 2016;44(5):327–346. doi:10.1615/CritRevBiomedEng.2017019768.
   PubMedGoogle Scholar
• Adam M, Schikowski T, Carsin AE, et al. Adult lung function and long-term air pollution exposure. ESCAPE: a multicentre cohort study and meta-analysis. Eur Respir J. 2015;45(1):38–50. doi:10.1183/09031936.00130014.
   PubMed Web of Science ®Google Scholar
• Clifford RL, Fishbane N, Patel J, et al. Altered DNA methylation is associated with aberrant gene expression in parenchymal but not airway fibroblasts isolated from individuals with COPD. Clin Epigenetics. 2018;10(1):32. doi:10.1186/s13148-018-0464-5.
   PubMedGoogle Scholar
• Salvi SS, Barnes PJ. Chronic obstructive pulmonary disease in non-smokers. Lancet. 2009;374(9691):733–743. doi:10.1016/S0140-6736(09)61303-9.
   PubMed Web of Science ®Google Scholar
• Gan WQ, FitzGerald JM, Carlsten C, et al. Associations of ambient air pollution with chronic obstructive pulmonary disease hospitalization and mortality. Am J Respir Crit Care Med. 2013;187(7):721–727. doi:10.1164/rccm.201211-2004OC.
   PubMed Web of Science ®Google Scholar
• Gershon A, Campitelli MA, Hwee J, et al. Socioeconomic status, sex, age and access to medications for COPD in Ontario, Canada. COPD. 2015;12(6):668–679. doi:10.3109/15412555.2015.1020148.
   PubMedGoogle Scholar
• Hazari YM, Bashir A, Habib M, et al. Alpha-1-antitrypsin deficiency: genetic variations, clinical manifestations and therapeutic interventions. Mutat Res. 2017;773:14–25. doi:10.1016/j.mrrev.2017.03.001.
   PubMed Web of Science ®Google Scholar
• Herriges M, Morrisey EE. Lung development: orchestrating the generation and regeneration of a complex organ. Development. 2014;141(3):502–513. doi:10.1242/dev.098186.
   PubMed Web of Science ®Google Scholar
• Park K-S, Korfhagen TR, Bruno MD, et al. SPDEF regulates goblet cell hyperplasia in the airway epithelium. J Clin Invest. 2007;117(4):978–988. doi:10.1172/JCI29176.
   PubMed Web of Science ®Google Scholar
• Tang X, Liu XJ, Tian C, et al. Foxa2 regulates leukotrienes to inhibit Th2-mediated pulmonary inflammation. Am J Respir Cell Mol Biol. 2013;49(6):960–970. doi:10.1165/rcmb.2013-0122OC.
   PubMed Web of Science ®Google Scholar
• Song J, Heijink I, Kistemaker L, et al. Aberrant DNA methylation and expression of SPDEF and FOXA2 in airway epithelium of patients with COPD. Clin Epigenetics. 2017;9(1):42. doi:10.1186/s13148-017-0341-7.
   PubMedGoogle Scholar
• Pfaff M, Powaga N, Akinci S, et al. Activation of the SPHK/S1P signalling pathway is coupled to muscarinic receptor-dependent regulation of peripheral airways. Respir Res. 2005;6(1):48. doi:10.1186/1465-9921-6-48.
   PubMedGoogle Scholar
• Barnawi J, Tran H, Jersmann H, et al. Potential link between the sphingosine-1-phosphate (S1P) system and defective alveolar macrophage phagocytic function in chronic obstructive pulmonary disease (COPD). PLoS One. 2015;10(10):e0122771. doi:10.1371/journal.pone.0122771.
   PubMed Web of Science ®Google Scholar
• Barnawi J, Jersmann H, Haberberger R, et al. Reduced DNA methylation of sphingosine-1 phosphate receptor 5 in alveolar macrophages in COPD: A potential link to failed efferocytosis. Respirology. 2017;22(2):315–321. doi:10.1111/resp.12949.
   PubMed Web of Science ®Google Scholar
• Sundar IK, Yin Q, Baier BS, et al. DNA methylation profiling in peripheral lung tissues of smokers and patients with COPD. Clin Epigenetics. 2017;9(1):38. doi:10.1186/s13148-017-0335-5.
   PubMedGoogle Scholar
• Liu J-P, Baker J, Perkins AS, et al. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell. 1993;75(1):59–72.
   PubMed Web of Science ®Google Scholar
• Epaud R, Aubey F, Xu J, et al. Knockout of insulin-like growth factor-1 receptor impairs distal lung morphogenesis. PLoS One. 2012;7(11):e48071. doi:10.1371/journal.pone.0048071.
   PubMed Web of Science ®Google Scholar
• Meyer KF, Krauss-Etschmann S, Kooistra W, et al. Prenatal exposure to tobacco smoke sex dependently influences methylation and mRNA levels of the Igf axis in lungs of mouse offspring. Am J Physiol Lung Cell Mol Physiol. 2017;312(4):L542–L555. doi:10.1152/ajplung.00271.2016.
   PubMed Web of Science ®Google Scholar
• Vucic EA, Chari R, Thu KL, et al. DNA methylation is globally disrupted and associated with expression changes in chronic obstructive pulmonary disease small airways. Am J Respir Cell Mol Biol. 2014;50(5):912–922. doi:10.1165/rcmb.2013-0304OC.
   PubMed Web of Science ®Google Scholar
• Adcock IM, Tsaprouni L, Bhavsar P, et al. Epigenetic regulation of airway inflammation. Curr Opin Immunol. 2007;19(6):694–700. doi:10.1016/j.coi.2007.07.016.
   PubMed Web of Science ®Google Scholar
• Szulakowski P, Crowther AJ, Jiménez LA, et al. The effect of smoking on the transcriptional regulation of lung inflammation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2006;174(1):41–50. doi:10.1164/rccm.200505-725OC.
   PubMed Web of Science ®Google Scholar
• Choudhary C, Kumar C, Gnad F, et al. Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009;325(5942):834–840. doi:10.1126/science.1175371.
   PubMed Web of Science ®Google Scholar
• Moresi V, Carrer M, Grueter CE, et al. Histone deacetylases 1 and 2 regulate autophagy flux and skeletal muscle homeostasis in mice. Proc Natl Acad Sci USA. 2012;109(5):1649–1654. doi:10.1073/pnas.1121159109.
   PubMed Web of Science ®Google Scholar
• Ding J, Li F, Cong Y, et al. Trichostatin A inhibits skeletal muscle atrophy induced by cigarette smoke exposure in mice. Life Sci. 2019;235:116800. doi:10.1016/j.lfs.2019.116800.
   PubMed Web of Science ®Google Scholar
• Blanc RS, Richard S. Arginine methylation: the coming of age. Mol Cell. 2017;65(1):8–24. doi:10.1016/j.molcel.2016.11.003.
   PubMed Web of Science ®Google Scholar
• Shin H-J, Kim H, Oh S, et al. AMPK-SKP2-CARM1 signalling cascade in transcriptional regulation of autophagy. Nature. 2016;534(7608):553–557. doi:10.1038/nature18014.
   PubMed Web of Science ®Google Scholar
• Kuhn P, Chumanov R, Wang Y, et al. Automethylation of CARM1 allows coupling of transcription and mRNA splicing. Nucleic Acids Res. 2011;39(7):2717–2726. doi:10.1093/nar/gkq1246.
   PubMed Web of Science ®Google Scholar
• Sarker RS, Conlon TM, Morrone C, et al. CARM1 regulates senescence during airway epithelial cell injury in COPD pathogenesis. Am J Physiol Lung Cell Mol Physiol. 2019;317(5):602–661. doi:10.1152/ajplung.00441.2018.
   PubMed Web of Science ®Google Scholar
• Sotty J, Garçon G, Denayer F-O, et al. Toxicological effects of ambient fine (PM2. 5-0.18) and ultrafine (PM0. 18) particles in healthy and diseased 3D organo-typic mucocilary-phenotype models. Environ Res. 2019;176:108538. doi:10.1016/j.envres.2019.108538.
   PubMed Web of Science ®Google Scholar
• López‐Campos JL, Tan W, Soriano JB. Global burden of COPD. Respirology. 2016;21(1):14–23. doi:10.1111/resp.12660.
   PubMed Web of Science ®Google Scholar
• Sundar IK, Yao H, Rahman I. Oxidative stress and chromatin remodeling in chronic obstructive pulmonary disease and smoking-related diseases. Antioxid Redox Signal. 2013;18(15):1956–1971. doi:10.1089/ars.2012.4863.
   PubMed Web of Science ®Google Scholar
• Kirkham PA, Barnes PJ. Oxidative stress in COPD. Chest. 2013;144(1):266–273. doi:10.1378/chest.12-2664.
   PubMed Web of Science ®Google Scholar
• Vachharajani VT, Liu T, Wang X, et al. Sirtuins link inflammation and metabolism. J Immunol Res. 2016;2016:8167273. doi:10.1155/2016/8167273.
   PubMed Web of Science ®Google Scholar
• Kim S-Y, Zhang Q, Brunmeir R, et al. SIRT1 Interacts with and Deacetylates ATP6V1B2 in Mature Adipocytes. PLoS One. 2015;10(7):e0133448. doi:10.1371/journal.pone.0133448.
   PubMed Web of Science ®Google Scholar
• Polesskaya A, Naguibneva I, Duquet A, et al. Interaction between acetylated MyoD and the bromodomain of CBP and/or p300. Mol Cell Biol. 2001;21(16):5312–5320. doi:10.1128/MCB.21.16.5312-5320.2001.
   PubMed Web of Science ®Google Scholar
• Ma N, Deng T-T, Wang Q, et al. Erythromycin regulates cigarette smoke-induced proinflammatory mediator release through sirtuin 1-nuclear factor κB axis in macrophages and mice lungs. Pathobiology. 2019;86(5–6):237–247. doi:10.1159/000500628.
   PubMed Web of Science ®Google Scholar
• Hwang J-w, Rajendrasozhan S, Yao H, et al. FOXO3 deficiency leads to increased susceptibility to cigarette smoke-induced inflammation, airspace enlargement, and chronic obstructive pulmonary disease. J Immunol. 2011;187(2):987–998. doi:10.4049/jimmunol.1001861.
   PubMed Web of Science ®Google Scholar
• Di Vincenzo S, Heijink IH, Noordhoek JA, et al. SIRT1/FoxO3 axis alteration leads to aberrant immune responses in bronchial epithelial cells. J Cell Mol Med. 2018;22(4):2272–2282. doi:10.1111/jcmm.13509.
   PubMed Web of Science ®Google Scholar
• Ito K, Hanazawa T, Tomita K, et al. Oxidative stress reduces histone deacetylase 2 activity and enhances IL-8 gene expression: role of tyrosine nitration. Biochem Biophys Res Commun. 2004;315(1):240–245. doi:10.1016/j.bbrc.2004.01.046.
   PubMed Web of Science ®Google Scholar
• Osoata GO, Yamamura S, Ito M, et al. Nitration of distinct tyrosine residues causes inactivation of histone deacetylase 2. Biochem Biophys Res Commun. 2009;384(3):366–371. doi:10.1016/j.bbrc.2009.04.128.
   PubMed Web of Science ®Google Scholar
• Chung K, Adcock I. Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction. Eur Respir J. 2008;31(6):1334–1356. doi:10.1183/09031936.00018908.
   PubMed Web of Science ®Google Scholar
• Ruan Y, Shen T, Wang Y, et al. Antimicrobial peptide LL-37 attenuates LTA induced inflammatory effect in macrophages. Int Immunopharmacol. 2013;15(3):575–580. doi:10.1016/j.intimp.2013.01.012.
   PubMed Web of Science ®Google Scholar
• Weng J-Z, Wang Y, Sun T-Y. Cathelicidin LL-37 restoring glucocorticoid function in smoking and lipopolysaccharide-induced airway inflammation in rats. Chin Med J. 2019;132(5):569.
   PubMed Web of Science ®Google Scholar
• Ichiyama T, Hasegawa S, Matsubara T, et al. Theophylline inhibits NF-kappa B activation and I kappa B alpha degradation in human pulmonary epithelial cells . Naunyn Schmiedebergs Arch Pharmacol. 2001;364(6):558–561. doi:10.1007/s00210-001-0494-x.
   PubMed Web of Science ®Google Scholar
• Yang S-R, Chida AS, Bauter MR, et al. Cigarette smoke induces proinflammatory cytokine release by activation of NF-kappaB and posttranslational modifications of histone deacetylase in macrophages . Am J Physiol Lung Cell Mol Physiol. 2006;291(1):L46–L57. doi:10.1152/ajplung.00241.2005.
   PubMed Web of Science ®Google Scholar
• Bin Y, Xiao Y, Huang D, et al. Theophylline inhibits cigarette smoke-induced inflammation in skeletal muscle by upregulating HDAC2 expression and decreasing NF-κB activation. Am J Physiol Lung Cell Mol Physiol. 2019;316(1):L197–L205. doi:10.1152/ajplung.00005.2018.
   PubMed Web of Science ®Google Scholar
• Yamamoto Y, Verma UN, Prajapati S, et al. Histone H3 phosphorylation by IKK-alpha is critical for cytokine-induced gene expression. Nature. 2003;423(6940):655–659. doi:10.1038/nature01576.
   PubMed Web of Science ®Google Scholar
• Redhu N, Gounni A. Function and mechanisms of TSLP/TSLPR complex in asthma and COPD. Clin Exp Allergy. 2012;42(7):994–1005. doi:10.1111/j.1365-2222.2011.03919.x.
   PubMed Web of Science ®Google Scholar
• Anzalone G, Albano GD, Montalbano AM, et al. IL-17A-associated IKK-α signaling induced TSLP production in epithelial cells of COPD patients. Exp Mol Med. 2018;50(10):1–12. doi:10.1038/s12276-018-0158-2.
   PubMedGoogle Scholar
• Gaffen SL. Structure and signalling in the IL-17 receptor family. Nat Rev Immunol. 2009;9(8):556–567. doi:10.1038/nri2586.
   PubMed Web of Science ®Google Scholar
• Doe C, Bafadhel M, Siddiqui S, et al. Expression of the T helper 17-associated cytokines IL-17A and IL-17F in asthma and COPD. Chest. 2010;138(5):1140–1147. doi:10.1378/chest.09-3058.
   PubMed Web of Science ®Google Scholar
• Lai T, Tian B, Cao C, et al. HDAC2 suppresses IL17A-mediated airway remodeling in human and experimental modeling of COPD. Chest. 2018;153(4):863–875. doi:10.1016/j.chest.2017.10.031.
   PubMed Web of Science ®Google Scholar
• Zeki AA, Franzi L, Last J, et al. Simvastatin inhibits airway hyperreactivity: implications for the mevalonate pathway and beyond. Am J Respir Crit Care Med. 2009;180(8):731–740. doi:10.1164/rccm.200901-0018OC.
   PubMed Web of Science ®Google Scholar
• Davis BB, Zeki AA, Bratt JM, et al. Simvastatin inhibits smoke-induced airway epithelial injury: implications for COPD therapy. Eur Respir J. 2013;42(2):350–361. doi:10.1183/09031936.00042512.
   PubMed Web of Science ®Google Scholar
• Matera MG, Calzetta L, Gritti G, et al. Role of statins and mevalonate pathway on impaired HDAC2 activity induced by oxidative stress in human airway epithelial cells. Eur J Pharmacol. 2018;832:114–119. doi:10.1016/j.ejphar.2018.05.023.
   PubMed Web of Science ®Google Scholar
• Barnes P, Adcock I, Ito K. Histone acetylation and deacetylation: importance in inflammatory lung diseases. Eur Respir J. 2005;25(3):552–563. doi:10.1183/09031936.05.00117504.
   PubMed Web of Science ®Google Scholar
• Barnes PJ, Adcock IM. Glucocorticoid resistance in inflammatory diseases. Lancet. 2009;373(9678):1905–1917. doi:10.1016/S0140-6736(09)60326-3.
   PubMed Web of Science ®Google Scholar
• Gan L, Li C, Wang J, et al. Curcumin modulates the effect of histone modification on the expression of chemokines by type II alveolar epithelial cells in a rat COPD model. COPD. 2016;11:2765–2773. doi:10.2147/COPD.S113978.
   Google Scholar
• Cheetham S, Gruhl F, Mattick J, et al. Long noncoding RNAs and the genetics of cancer. Br J Cancer. 2013;108(12):2419–2425. doi:10.1038/bjc.2013.233.
   PubMed Web of Science ®Google Scholar
• Qu X, Dang X, Wang W, et al. Long noncoding RNAs and mRNA regulation in peripheral blood mononuclear cells of patients with chronic obstructive pulmonary disease. Mediat Inflamm. 2018;2018:1–14. doi:10.1155/2018/7501851.
   Web of Science ®Google Scholar
• Qi X, Chen H, Fu B, et al. lncrnas nr-026690 and ensT00000447867 are upregulated in CD4+ T cells in patients with acute exacerbation of COPD. COPD. 2019;14:699–711. doi:10.2147/COPD.S191815.
   Google Scholar
• Nair GB, Niederman MS. Ventilator-associated pneumonia: present understanding and ongoing debates. Intensive Care Med. 2015;41(1):34–48. doi:10.1007/s00134-014-3564-5.
   PubMed Web of Science ®Google Scholar
• Nseir S, Di Pompeo C, Soubrier S, et al. Impact of ventilator-associated pneumonia on outcome in patients with COPD. Chest. 2005;128(3):1650–1656. doi:10.1378/chest.128.3.1650.
   PubMed Web of Science ®Google Scholar
• Zhao X, Feng J, Zhang L, et al. One functional variant in the 3′‐untranslated region of TLR4 is associated with the elevated risk of ventilator‐associated pneumonia in the patients with chronic obstructive pulmonary disease. J Cell Physiol. 2019;234(10):18879–18886. doi:10.1002/jcp.28526.
   PubMed Web of Science ®Google Scholar
• Jalali S, Ramanathan GK, Parthasarathy PT, et al. Mir-206 regulates pulmonary artery smooth muscle cell proliferation and differentiation. PLoS One. 2012;7(10):e46808. doi:10.1371/journal.pone.0046808.
   PubMed Web of Science ®Google Scholar
• Donaldson A, Natanek SA, Lewis A, et al. Increased skeletal muscle-specific microRNA in the blood of patients with COPD. Thorax. 2013;68(12):1140–1149. doi:10.1136/thoraxjnl-2012-203129.
   PubMed Web of Science ®Google Scholar
• Sun Y, An N, Li J, et al. miRNA-206 regulates human pulmonary microvascular endothelial cell apoptosis via targeting in chronic obstructive pulmonary disease. J Cell Biochem. 2019;120(4):6223–6236. doi:10.1002/jcb.27910.
   PubMed Web of Science ®Google Scholar
• Cai S, Chen P, Zhang C, et al. Oral N-acetylcysteine attenuates pulmonary emphysema and alveolar septal cell apoptosis in smoking-induced COPD in rats. Respirology. 2009;14(3):354–359. doi:10.1111/j.1440-1843.2009.01511.x.
   PubMed Web of Science ®Google Scholar
• Long Y-J, Liu X-P, Chen S-S, et al. miR-34a is involved in CSE-induced apoptosis of human pulmonary microvascular endothelial cells by targeting Notch-1 receptor protein. Respir Res. 2018;19(1):21. doi:10.1186/s12931-018-0722-2.
   PubMed Web of Science ®Google Scholar
• Takada H, Kurisaki A. Emerging roles of nucleolar and ribosomal proteins in cancer, development, and aging. Cell Mol Life Sci. 2015;72(21):4015–4025. doi:10.1007/s00018-015-1984-1.
   PubMed Web of Science ®Google Scholar
• Wolfe RR. The underappreciated role of muscle in health and disease. Am J Clin Nutr. 2006;84(3):475–482. doi:10.1093/ajcn/84.3.475.
   PubMed Web of Science ®Google Scholar
• He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5(7):522–531. doi:10.1038/nrg1379.
   PubMed Web of Science ®Google Scholar
• Connolly M, Paul R, Farre‐Garros R, et al. miR-424-5p reduces ribosomal RNA and protein synthesis in muscle wasting. J Cachexia Sarcopenia Muscle. 2018;9(2):400–416. doi:10.1002/jcsm.12266.
   PubMed Web of Science ®Google Scholar
• Yao J, Liang L-h, Zhang Y, et al. GNAI1 suppresses tumor cell migration and invasion and is post-transcriptionally regulated by Mir-320a/c/d in hepatocellular carcinoma. Cancer Biol Med. 2012;9(4):234–241. doi:10.7497/j.issn.2095-3941.2012.04.003.
   PubMedGoogle Scholar
• Karch A, COSYCONET Study Group, Vogelmeier C, Welte T, et al. The German COPD cohort COSYCONET: Aims, methods and descriptive analysis of the study population at baseline. Respir Med. 2016;114:27–37. doi:10.1016/j.rmed.2016.03.008.
   PubMed Web of Science ®Google Scholar
• Sekine Y, Katsura H, Koh E, et al. Early detection of COPD is important for lung cancer surveillance. Eur Respir J. 2012;39(5):1230–1240. doi:10.1183/09031936.00126011.
   PubMed Web of Science ®Google Scholar
• Keller A, Ludwig N, Fehlmann T, et al. Low miR-150-5p and miR-320b Expression Predicts Reduced Survival of COPD Patients. Cell J. 2019;8(10):1162. doi:10.3390/cells8101162.
   Web of Science ®Google Scholar
• Taganov KD, Boldin MP, Chang K-J, et al. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA. 2006;103(33):12481–12486. doi:10.1073/pnas.0605298103.
   PubMed Web of Science ®Google Scholar
• Mohamed A, Pekoz AY, Ross K, et al. Pulmonary delivery of Nanocomposite Microparticles (NCMPs) incorporating miR-146a for treatment of COPD. Int J Pharm. 2019;569:118524. doi:10.1016/j.ijpharm.2019.118524.
   PubMed Web of Science ®Google Scholar
• Putra AC, Tanimoto K, Arifin M, et al. Genetic variations in detoxification enzymes and HIF-1α in Japanese patients with COPD. Clin Respir J. 2013;7(1):7–15. doi:10.1111/j.1752-699X.2011.00255.x.
   PubMed Web of Science ®Google Scholar
• Cai J, Wu J, Zhang H, et al. miR-186 downregulation correlates with poor survival in lung adenocarcinoma, where it interferes with cell-cycle regulation. Cancer Res. 2013;73(2):756–766. doi:10.1158/0008-5472.CAN-12-2651.
   PubMed Web of Science ®Google Scholar
• Lin L, Sun J, Wu D, et al. MicroRNA-186 is associated with hypoxia-inducible factor-1α expression in chronic obstructive pulmonary disease . Mol Genet Genomic Med. 2019;7(3):e531. doi:10.1002/mgg3.531.
   PubMed Web of Science ®Google Scholar
• Hassan F, Xu X, Nuovo G, et al. Accumulation of metals in GOLD4 COPD lungs is associated with decreased CFTR levels. Respir Res. 2014;15(1):69. doi:10.1186/1465-9921-15-69.
   PubMedGoogle Scholar
• Asker S, Asker M, Yeltekin AC, et al. Serum levels of trace minerals and heavy metals in severe COPD patients with and without pulmonary hypertension. Int J Chron Obstruct Pulmon Dis. 2018;13:1803–1808. doi:10.2147/COPD.S164431.
   PubMed Web of Science ®Google Scholar
• Kim J, Kim DY, Heo H-R, et al. Role of miRNA-181a-2-3p in cadmium-induced inflammatory responses of human bronchial epithelial cells. J Thorac Dis. 2019;11(7):3055–3069. doi:10.21037/jtd.2019.07.55.
   PubMed Web of Science ®Google Scholar
• Santos S, Peinado VI, Ramirez J, et al. Characterization of pulmonary vascular remodelling in smokers and patients with mild COPD. Eur Respir J. 2002;19(4):632–638. doi:10.1183/09031936.02.00245902.
   PubMed Web of Science ®Google Scholar
• Nazari-Jahantigh M, Wei Y, Schober A. The role of microRNAs in arterial remodelling. Thromb Haemost. 2012;107(4):611–618. doi:10.1160/TH11-12-0826.
   PubMed Web of Science ®Google Scholar
• Musri MM, Coll-Bonfill N, Maron BA, et al. MicroRNA Dysregulation in Pulmonary Arteries from Chronic Obstructive Pulmonary Disease. Relationships with Vascular Remodeling. Am J Respir Cell Mol Biol. 2018;59(4):490–499. doi:10.1165/rcmb.2017-0040OC.
   PubMed Web of Science ®Google Scholar
• Stafford JL, Neumann NF, Belosevic M. Macrophage-mediated innate host defense against protozoan parasites. Crit Rev Microbiol. 2002;28(3):187–248. doi:10.1080/1040-840291046731.
   PubMed Web of Science ®Google Scholar
• Vlahos R, Bozinovski S. Role of alveolar macrophages in chronic obstructive pulmonary disease. Front Immunol. 2014;5:435. doi:10.3389/fimmu.2014.00435.
   PubMed Web of Science ®Google Scholar
• Caito S, Yang S-R, Kode A, et al. Rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2, PPARgamma agonists, differentially regulate cigarette smoke-mediated pro-inflammatory cytokine release in monocytes/macrophages. Antioxid Redox Signal. 2008;10(2):253–260. doi:10.1089/ars.2007.1889.
   PubMed Web of Science ®Google Scholar
• Wang D, He S, Liu B, et al. MiR-27-3p regulates TLR2/4-dependent mouse alveolar macrophage activation by targetting PPARγ. Clin Sci. 2018;132(9).
   Web of Science ®Google Scholar
• Togo S, Holz O, Liu X, et al. Lung fibroblast repair functions in patients with chronic obstructive pulmonary disease are altered by multiple mechanisms. Am J Respir Crit Care Med. 2008;178(3):248–260. doi:10.1164/rccm.200706-929OC.
   PubMed Web of Science ®Google Scholar
• Ikari J, Smith LM, Nelson AJ, et al. Effect of culture conditions on microRNA expression in primary adult control and COPD lung fibroblasts in vitro. In Vitro Cell Dev Biol Anim. 2015;51(4):390–399. doi:10.1007/s11626-014-9820-8.
   PubMed Web of Science ®Google Scholar
• Ikari J, Nelson AJ, Obaid J, et al. Reduced microRNA-503 expression augments lung fibroblast VEGF production in chronic obstructive pulmonary disease. PLoS One. 2017;12(9):e0184039. doi:10.1371/journal.pone.0184039.
   PubMed Web of Science ®Google Scholar
• Shen Z, Tang W, Guo J, et al. miR-483-5p plays a protective role in chronic obstructive pulmonary disease. Int J Mol Med. 2017;40(1):193–200. doi:10.3892/ijmm.2017.2996.
   PubMed Web of Science ®Google Scholar
• Leidinger P, Keller A, Borries A, et al. Specific peripheral miRNA profiles for distinguishing lung cancer from COPD. Lung Cancer. 2011;74(1):41–47. doi:10.1016/j.lungcan.2011.02.003.
   PubMed Web of Science ®Google Scholar
• Shaw JG, Vaughan A, Dent AG, et al. Biomarkers of progression of chronic obstructive pulmonary disease (COPD). J Thorac Dis. 2014;6(11):1532–1547. doi:10.3978/j.issn.2072-1439.2014.11.33.
   PubMed Web of Science ®Google Scholar
• Wang R, Xu J, Liu H, et al. Peripheral leukocyte microRNAs as novel biomarkers for COPD. Int J Chron Obstruct Pulmon Dis. 2017;12:1101–1112. doi:10.2147/COPD.S130416.
   PubMed Web of Science ®Google Scholar
• Conickx G, Mestdagh P, Avila Cobos F, et al. MicroRNA profiling reveals a role for microRNA-218-5p in the pathogenesis of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2017;195(1):43–56. doi:10.1164/rccm.201506-1182OC.
   PubMed Web of Science ®Google Scholar