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Commentary

Epithelial–mesenchymal transition is driven by transcriptional and post transcriptional modulations in COPD: implications for disease progression and new therapeutics

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Pages 1603-1610 | Published online: 18 Jul 2019

References

  • WHO. World Health. Organisation, chronic obstructive pulmonary disease (COPD)- key facts. 2016 Available from: http://wwwwhoint/news-room/fact-sheets/detail/chronic-obstructive-pulmonary-disease-(copd).
  • Lee JJ, Liu D, Lee JS, et al. Long-term impact of smoking on lung epithelial proliferation in current and former smokers. J Natl Cancer Inst. 2001;93(14):1081–1088. doi:10.1093/jnci/93.14.108111459869
  • Eapen MS, Myers S, Walters EH, Sohal SS. Airway inflammation in chronic obstructive pulmonary disease (COPD): a true paradox. Expert Rev Respir Med. 2017;11(10):827–839. doi:10.1080/17476348.2017.136076928743228
  • Peters EJ, Morice R, Benner SE, et al. Squamous metaplasia of the bronchial mucosa and its relationship to smoking. Chest. 1993;103(5):1429–1432. doi:10.1378/chest.103.5.14298486022
  • Ojo O, Lagan AL, Rajendran V, et al. Pathological changes in the COPD lung mesenchyme - Novel lessons learned from in vitro and in vivo studies. Pulm Pharmacol Ther. 2014. doi:10.1016/j.pupt.2014.04.004
  • Makita H, Nasuhara Y, Nagai K, et al. Characterisation of phenotypes based on severity of emphysema in chronic obstructive pulmonary disease. Thorax. 2007;62(11):932–937. doi:10.1136/thx.2006.07277717573447
  • American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1995;152(5 Pt 2):S77–S121.7582322
  • Koo HK, Vasilescu DM, Booth S, et al. Small airways disease in mild and moderate chronic obstructive pulmonary disease: a cross-sectional study. Lancet Respir Med. 2018;6(8):591–602.30072106
  • Kirby M, Tanabe N, Tan WC, et al. Total airway count on computed tomography and the risk of chronic obstructive pulmonary disease progression. findings from a population-based study. Am J Respir Crit Care Med. 2018;197(1):56–65.28886252
  • Hallstrand TS, Hackett TL, Altemeier WA, Matute-Bello G, Hansbro PM, Knight DA. Airway epithelial regulation of pulmonary immune homeostasis and inflammation. Clin Immunol (orlando, Fla). 2014;151(1):1–15. doi:10.1016/j.clim.2013.12.003
  • Moheimani F, Roth HM, Cross J, et al. Disruption of beta-catenin/CBP signaling inhibits human airway epithelial-mesenchymal transition and repair. Int J Biochem Cell Biol. 2015;68:59–69. doi:10.1016/j.biocel.2015.08.01426315281
  • Puchelle E, Zahm JM, Tournier JM, Coraux C. Airway epithelial repair, regeneration, and remodeling after injury in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2006;3(8):726–733. doi:10.1513/pats.200605-126SF17065381
  • Aghapour M, Raee P, Moghaddam SJ, Hiemstra PS, Heijink IH. Airway epithelial barrier dysfunction in chronic obstructive pulmonary disease: role of cigarette smoke exposure. Am J Respir Cell Mol Biol. 2018;58(2):157–169. doi:10.1165/rcmb.2017-0200TR28933915
  • Shaykhiev R, Crystal RG. Early events in the pathogenesis of chronic obstructive pulmonary disease. smoking-induced reprogramming of airway epithelial basal progenitor cells. Ann Am Thorac Soc. 2014;11(Suppl 5):S252–S258. doi:10.1513/AnnalsATS.201402-049AW25525728
  • Shaykhiev R, Otaki F, Bonsu P, et al. Cigarette smoking reprograms apical junctional complex molecular architecture in the human airway epithelium in vivo. Cell Mol Life Sci. 2011;68(5):877–892. doi:10.1007/s00018-010-0500-x20820852
  • Sohal SS. Airway basal cell reprogramming and EMT: potential key to understanding early COPD. Am J Respir Crit Care Med. 2018;197:1644–1645. doi:10.1164/rccm.201712-2450LE29385350
  • Nowrin K, Sohal SS, Peterson G, Patel R, Walters EH. Epithelial-mesenchymal transition as a fundamental underlying pathogenic process in COPD airways: fibrosis, remodeling and cancer. Expert Rev Respir Med. 2014;8(5):547–559. doi:10.1586/17476348.2014.94885325113142
  • Sohal SS. Endothelial to mesenchymal transition (EndMT): an active process in Chronic Obstructive Pulmonary Disease (COPD)? Respir Res. 2016;17(1):20. doi:10.1186/s12931-016-0337-426898357
  • Königshoff M. Lung cancer in pulmonary fibrosis: tales of epithelial cell plasticity. Respiration. 2011;81(5):353–358. doi:10.1159/00032629921502777
  • Kumar JM, Chris W, Suji EM, et al. Epithelial–mesenchymal transition, a spectrum of states: role in lung development, homeostasis, and disease. Develop Dyn. 2018;247(3):346–358. doi:10.1002/dvdy.24541
  • Gurzu S, Turdean S, Kovecsi A, Contac AO, Jung I. Epithelial-mesenchymal, mesenchymal-epithelial, and endothelial-mesenchymal transitions in malignant tumors: an update. World J Clin Cases. 2015;3:393. doi:10.12998/wjcc.v3.i5.39325984514
  • Sohal SS, Walters EH. Advanced non-small-cell lung cancer. N Engl J Med. 2017;377(20):1998–1999. doi:10.1056/NEJMc1712794
  • Milara J, Peiró T, Serrano A, Cortijo J. Epithelial to mesenchymal transition is increased in patients with COPD and induced by cigarette smoke. Thorax. 2013;68(5):410–420. doi:10.1136/thoraxjnl-2012-20176123299965
  • Sohal SS, Reid D, Soltani A, et al. Evaluation of epithelial mesenchymal transition in patients with chronic obstructive pulmonary disease. Respir Res. 2011;12. doi:10.1186/1465-9921-12-130
  • Sohal SS, Walters EH. Epithelial mesenchymal transition (EMT) in small airways of COPD patients. Thorax. 2013;68:783–784. doi:10.1136/thoraxjnl-2013-20337323492370
  • Mahmood MQ, Sohal SS, Shukla SD, et al. Epithelial mesenchymal transition in smokers: large versus small airways and relation to airflow obstruction. Int J Chron Obstruct Pulmon Dis. 2015;10:1515–1524.26346976
  • Sohal SS. Chronic obstructive pulmonary disease (COPD) and lung cancer: epithelial mesenchymal transition (EMT), the missing link? EBioMedicine. 2015;2:1578–1579. doi:10.1016/j.ebiom.2015.10.01626870773
  • Sohal S, Reid D, Soltani A, et al. Reticular basement membrane fragmentation and potential epithelial mesenchymal transition is exaggerated in the airways of smokers with chronic obstructive pulmonary disease. Respirology. 2010;15(6):930–938. doi:10.1111/j.1440-1843.2010.01808.x20630030
  • Schneider M, Hansen JL, Sheikh SP. S100A4: a common mediator of epithelial-mesenchymal transition, fibrosis and regeneration in diseases?. J Mol Med. 2008;86:507–522. doi:10.1007/s00109-007-0301-318322670
  • Sohal SS, Soltani A, Weston S, Wood-Baker R, Walters H. Intermediate filament vimentin and potential role in epithelial mesenchymal transition (EMT). Vimentin Concepts Mol Mech. 2013.
  • Sohal SS, Reid D, Soltani A, et al. Reticular basement membrane fragmentation and potential epithelial mesenchymal transition is exaggerated in the airways of smokers with chronic obstructive pulmonary disease. Respirology. 2010;15:930–938. doi:10.1111/j.1440-1843.2010.01808.x20630030
  • Soltani A, Walters EH, Reid DW, et al. Inhaled corticosteroid normalizes some but not all airway vascular remodeling in COPD. Int J Chron Obstruct Pulmon Dis. 2016;11:2359–2367. doi:10.2147/COPD.S11317627703346
  • Sohal SS, Reid D, Soltani A, Ward C, Weston S, Muller HK. Reticular basement membrane fragmentation and potential epithelial mesenchymal transition is exaggerated in the airways of smokers with chronic obstructive pulmonary disease. Respirology. 2010;15:930–938.20630030
  • Soltani A, Reid DW, Sohal SS, et al. Basement membrane and vascular remodelling in smokers and chronic obstructive pulmonary disease: a cross-sectional study. Respir Res. 2010;11(1):105. doi:10.1186/1465-9921-11-6220670454
  • Sohal SS, Soltani A, Reid D, et al. A randomized controlled trial of inhaled corticosteroids (ICS) on markers of epithelial-mesenchymal transition (EMT) in large airway samples in COPD: an exploratory proof of concept study. Int J Chron Obstruct Pulmon Dis. 2014;9. doi:10.2147/COPD.S60179
  • Sohal SS, Mahmood QM, Walters HE. Clinical significance of epithelial mesenchymal transition (EMT) in chronic obstructive pulmonary disease (COPD): potential target for prevention of airway fibrosis and lung cancer. Clin Transl Med. 2014;3. doi:10.1186/s40169-014-0033-2
  • Raymakers AJ, McCormick N, Marra CA, Fitzgerald JM, Sin D, Lynd LD. Do inhaled corticosteroids protect against lung cancer in patients with COPD? A systematic review. Respirology. 2017;22(1):61–70. doi:10.1111/resp.1291927761973
  • Milara J, Peiro T, Serrano A, et al. Roflumilast N-oxide inhibits bronchial epithelial to mesenchymal transition induced by cigarette smoke in smokers with COPD. Pulm Pharmacol Ther. 2014;28(2):138–148. doi:10.1016/j.pupt.2014.02.00124525294
  • Gohy ST, Hupin C, Fregimilicka C, et al. Imprinting of the COPD airway epithelium for dedifferentiation and mesenchymal transition. Eur Respir J. 2015. doi:10.1183/09031936.00135814
  • Wang Q, Wang Y, Zhang Y, Zhang Y, Xiao W. The role of uPAR in epithelial-mesenchymal transition in small airway epithelium of patients with chronic obstructive pulmonary disease. Respir Res. 2013;14(1):67. doi:10.1186/1465-9921-14-1923806081
  • Froidure A, Ladjemi MZ, Pilette C. Interleukin-1α: a key player for epithelial-to-mesenchymal signalling in COPD? Eur Respir J. 2016;48(2):301–304. doi:10.1183/13993003.01180-201627478185
  • Osei ET, Noordhoek JA, Hackett TL, et al. Interleukin-1alpha drives the dysfunctional cross-talk of the airway epithelium and lung fibroblasts in COPD. Eur Respir J. 2016;48(2):359–369. doi:10.1183/13993003.01911-201527418555
  • Soltani A, Sohal S, Reid D, Weston S, Wood-Baker R, Walters E. Vessel-associated transforming growth factor-Beta1 (TGF-beta1) is increased in the bronchial reticular basement membrane in COPD and normal smokers. PLoS One. 2012;7(6):e39736. doi:10.1371/journal.pone.003973622768115
  • Mahmood MQ, Reid D, Ward C, et al. Transforming growth factor (TGF) beta1 and Smad signalling pathways: a likely key to EMT-associated COPD pathogenesis. Respirology. 2017;22(1):133–140. doi:10.1111/resp.1288227614607
  • Springer J, Scholz FR, Peiser C, Groneberg DA, Fischer A. SMAD-signaling in chronic obstructive pulmonary disease: transcriptional down-regulation of inhibitory SMAD 6 and 7 by cigarette smoke. Biol Chem. 2004;385(7):649–653. doi:10.1515/BC.2004.08015318814
  • Zandvoort A, Postma DS, Jonker MR, et al. Altered expression of the Smad signalling pathway: implications for COPD pathogenesis. Eur Respir J. 2006;28(3):533–541. doi:10.1183/09031936.06.0007840516707515
  • Verhamme FM, Bracke KR, Joos GF, Brusselle GG. Transforming growth factor-β superfamily in obstructive lung diseases. more suspects than TGF-β alone. Am J Respir Cell Mol Biol. 2015;52(6):653–662. doi:10.1165/rcmb.2014-0282RT25396302
  • Mahmood MQ, Walters EH, Shukla SD, et al. β-catenin, twist and snail: transcriptional regulation of EMT in smokers and COPD, and relation to airflow obstruction. Sci Rep. 2017;7(1):10832. doi:10.1038/s41598-017-11375-x28883453
  • Zou W, Zou Y, Zhao Z, Li B, Ran P. Nicotine-induced epithelial-mesenchymal transition via Wnt/beta-catenin signaling in human airway epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2013;304(4):L199–L209. doi:10.1152/ajplung.00094.201223204070
  • Kneidinger N, AÖ Y, Callegari J, et al. Activation of the WNT/β-catenin pathway attenuates experimental emphysema. Am J Respir Crit Care Med. 2011;183(6):723–733. doi:10.1164/rccm.200910-1560OC20889911
  • Skronska-Wasek W, Mutze K, Baarsma HA, et al. Reduced frizzled receptor 4 expression prevents WNT/β-catenin–driven alveolar lung repair in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2017;196(2):172–185. doi:10.1164/rccm.201605-0904OC28245136
  • Baarsma HA, Königshoff M. ‘WNT-er is coming’: WNT signalling in chronic lung diseases. Thorax. 2017;72(8):746–759. doi:10.1136/thoraxjnl-2016-20975328416592
  • Heijink IH, de Bruin HG, Dennebos R, et al. Cigarette smoke-induced epithelial expression of WNT-5B: implications for COPD. Eur Respir J. 2016;48(2):504–515. doi:10.1183/13993003.01541-201527126693
  • DiRenzo DM, Chaudhary MA, Shi X, et al. A crosstalk between TGF-β/Smad3 and Wnt/β-catenin pathways promotes vascular smooth muscle cell proliferation. Cell Signal. 2016;28(5):498–505. doi:10.1007/s12032-017-0900-y26912210
  • Zhou B, Liu Y, Kahn M, et al. Interactions between β-catenin and transforming growth factor-β signaling pathways mediate epithelial-mesenchymal transition and are dependent on the transcriptional co-activator cAMP-response element-binding protein (CREB)-binding protein (CBP). J Biol Chem. 2012;287(10):7026–7038. doi:10.1074/jbc.M111.27631122241478
  • Jiang B, Guan Y, Shen H-J, et al. Akt/PKB signaling regulates cigarette smoke-induced pulmonary epithelial-mesenchymal transition. Lung Cancer. 2018;122:44–53. doi:10.1016/j.lungcan.2018.05.01930032844
  • Lai T, Li Y, Chen M, et al. Heparin-binding epidermal growth factor contributes to COPD disease severity by modulating airway fibrosis and pulmonary epithelial-mesenchymal transition. Lab Invest. 2018;98(9):1159–1169. doi:10.1038/s41374-018-0049-029581578
  • Eapen MS, Sharma P, Thompson IE, et al. Heparin-binding epidermal growth factor (HB-EGF) drives EMT in patients with COPD: implications for disease pathogenesis and novel therapies. Lab Invest. 2019;99(2):150–157. doi:10.1038/s41374-018-0146-030451982
  • Sun J, Gu X, Wu N, Zhang P, Liu Y, Jiang S. Human antigen R enhances the epithelial-mesenchymal transition via regulation of ZEB-1 in the human airway epithelium. Respir Res. 2018;19. doi:10.1186/s12931-018-0805-0
  • Zhou Y, Chang R, Ji W, et al. Loss of scribble promotes snail translation through translocation of HuR and enhances cancer drug resistance. J Biol Chem. 2016;291(1):291–302. doi:10.1074/jbc.M115.69385326527679
  • Gu XM, Wang XG, Sun J, Wang N, Jiang SJ. The role of HuR in mediating snail expression in human small airway epithelium induced by cigarette smoke extract. Zhonghua Jie He He Hu Xi Za Zhi. 2017;40(7):515–519. doi:10.3760/cma.j.issn.1001-0939.2017.07.00828728276
  • Kim I, Hur J, Jeong S. HuR represses Wnt/β-catenin-mediated transcriptional activity by promoting cytoplasmic localization of β-catenin. Biochem Biophys Res Commun. 2015;457(1):65–70. doi:10.1016/j.bbrc.2014.12.05225534855
  • Sohal SS, Hansbro PM, Walters EH. Epithelial mesenchymal transition in chronic obstructive pulmonary disease, a precursor for epithelial cancers: understanding and translation to early therapy. Ann Am Thorac Soc. 2017;14(9):1491–1492. doi:10.1513/AnnalsATS.201705-387LE28594567
  • Sohal SS. Chronic Obstructive Pulmonary Disease (COPD) and lung cancer: epithelial mesenchymal transition (EMT), the missing link? EBioMedicine. 2015;2(11):1578–1579. doi:10.1016/j.ebiom.2015.10.01626870773
  • Mahmood MQ, Ward C, Muller HK, Sohal SS, Walters EH. Epithelial mesenchymal transition (EMT) and non-small cell lung cancer (NSCLC): a mutual association with airway disease. Med Oncol. 2017;34(3):45.28197929
  • Sohal SS, Eapen MS, Ward C, Walters EH. Epithelial mesenchymal transition (EMT): a necessary new therapeutic target in COPD? Am J Respir Crit Care Med. 2017. doi:10.1164/rccm.201704-0771LE
  • Andersson-Sjöland A, Nihlberg K, Eriksson L, Bjermer L, Westergren-Thorsson G. Fibrocytes and the tissue niche in lung repair. Respir Res. 2011;12(1):76. doi:10.1186/1465-9921-12-12221658209
  • Sohal SS. Epithelial and endothelial cell plasticity in chronic obstructive pulmonary disease (COPD). Respir Investig. 2017;55(2):104–113.
  • Eapen MS, Myers S, Lu W, Tanghe C, Sharma P, Sohal SS. sE-cadherin and sVE-cadherin indicate active epithelial/endothelial to mesenchymal transition (EMT and EndoMT) in smokers and COPD: implications for new biomarkers and therapeutics. Biomarkers. 2018;23:1–5.29144175
  • Burgess JK, Mauad T, Tjin G, Karlsson JC, Westergren‐Thorsson G. The extracellular matrix – the under‐recognized element in lung disease? J Pathol. 2016;240(4):397–409.27623753
  • Baarsma HA, Spanjer AIR, Haitsma G, et al. Activation of WNT/β-catenin signaling in pulmonary fibroblasts by TGF-β1 is increased in chronic obstructive pulmonary disease. PLoS One. 2011;6(9):e25450.21980461
  • Akhmetshina A, Palumbo K, Dees C, et al. Activation of canonical Wnt signalling is required for TGF-β-mediated fibrosis. Nat Commun. 2012;3:735.22415826
  • Al-Habeeb FF, Nair PK, Azuelos I, Baglole C. The role of HuR in myofibroblast differentiation: implication for pulmonary fibrosis. A68 molecular determinants of remodeling in lung fibrosis. Am Thorac Soc Int Conf Abstr. 2018;197:A2205–A.
  • Eapen MS, Sohal SS. Understanding novel mechanisms of microbial pathogenesis in chronic lung disease: implications for new therapeutic targets. Clin Sci (Lond). 2018;132(3):375–379.29439118
  • Sohal SS. Inhaled corticosteroids and increased microbial load in COPD: potential role of epithelial adhesion molecules. Eur Respir J. 2018;51(2):1702257.29386338
  • Sohal SS, Eapen MS, Ward C, Walters EH. Airway inflammation and inhaled corticosteroids in COPD. Eur Respir J. 2017;49(6):1700289.28619960
  • Eapen MS, McAlinden K, Tan D, et al. Profiling cellular and inflammatory changes in the airway wall of mild to moderate COPD. Respirology. 2017;22(6):1125–1132.28326668
  • Eapen MS, Hansbro PM, McAlinden K, et al. Abnormal M1/M2 macrophage phenotype profiles in the small airway wall and lumen in smokers and chronic obstructive pulmonary disease (COPD). Sci Rep. 2017;7(1):13392.29042607
  • Zhu L, Fu X, Chen X, Han X, Dong P. M2 macrophages induce EMT through the TGF-beta/Smad2 signaling pathway. Cell Biol Int. 2017;41(9):960–968.28493530
  • Yu CC, Chien CT, Chang TC. M2 macrophage polarization modulates epithelial-mesenchymal transition in cisplatin-induced tubulointerstitial fibrosis. BioMedicine. 2016;6(1):5.26872813
  • Braga TT, Agudelo JSH, Camara NOS. Macrophages during the fibrotic process: M2 as friend and foe. Front Immunol. 2015;6:602.26635814
  • Eapen MS, Sharma P, Moodley YP, Hansbro PM, Sohal SS. Dysfunctional immunity and microbial adhesion molecules in smoking-induced pneumonia. Am J Respir Crit Care Med. 2018;199:250–251.
  • Jubrail J, Kurian N, Niedergang F. Macrophage phagocytosis cracking the defect code in COPD. Biomed J. 2017;40(6):305–312.29433833
  • McKendry RT, Spalluto CM, Burke H, et al. Dysregulation of antiviral function of CD8(+) T cells in the chronic obstructive pulmonary disease lung. role of the PD-1-PD-L1 axis. Am J Respir Crit Care Med. 2016;193(6):642–651.26517304
  • Yiakouvaki A, Dimitriou M, Karakasiliotis I, Eftychi C, Theocharis S, Kontoyiannis DL. Myeloid cell expression of the RNA-binding protein HuR protects mice from pathologic inflammation and colorectal carcinogenesis. J Clin Invest. 2012;122(1):48–61.22201685
  • Katsanou V, Papadaki O, Milatos S, et al. HuR as a negative posttranscriptional modulator in inflammation. Mol Cell. 2005;19(6):777–789.16168373
  • Eapen MS, Hansbro PM, Larsson-Callerfelt AK, et al. Chronic obstructive pulmonary disease and lung cancer: underlying pathophysiology and new therapeutic modalities. Drugs. 2018;78(16):1717–1740.30392114
  • Sohal SS, Walters EH. Essential need for rethink of COPD airway pathology: implications for new drug approaches for prevention of lung cancer as well as small airway fibrosis. Int J Chron Obstruct Pulmon Dis. 2017;12:2677–2679.28919735