Display options
Share it on

Int J Chron Obstruct Pulmon Dis. 2019 Jul 18;14:1603-1610. doi: 10.2147/COPD.S208428. eCollection 2019.

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

International journal of chronic obstructive pulmonary disease

Mathew Suji Eapen, Pawan Sharma, Archana Vijay Gaikwad, Wenying Lu, Stephen Myers, Philip M Hansbro, Sukhwinder Singh Sohal

Affiliations

  1. Respiratory Translational Research Group, Department of Laboratory Medicine, College of Health and Medicine, University of Tasmania, Launceston, TAS 7248, Australia.
  2. Medical Sciences, University of Technology Sydney, Sydney, NSW 2007, Australia.
  3. Woolcock Emphysema Centre, Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW 2037, Australia.
  4. Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and the University of Newcastle, Newcastle, NSW 2308, Australia.
  5. Centre for Inflammation, Centenary Institute and University of Technology Sydney, Sydney, NSW 2007, Australia.

PMID: 31409985 PMCID: PMC6645357 DOI: 10.2147/COPD.S208428

Abstract

COPD is a common and highly destructive disease with huge impacts on people and health services throughout the world. It is mainly caused by cigarette smoking though environmental pollution is also significant. There are no current treatments that affect the overall course of COPD; current drugs focus on symptomatic relief and to some extent reducing exacerbation rates. There is an urgent need for in-depth studies of the fundamental pathogenic mechanisms that underpin COPD. This is vital, given the fact that nearly 40%-60% of the small airway and alveolar damage occurs in COPD well before the first measurable changes in lung function are detected. These individuals are also at a high risk of lung cancer. Current COPD research is mostly centered around late disease and/or innate immune activation within the airway lumen, but the actual damage to the airway wall has early onset. COPD is the end result of complex mechanisms, possibly triggered through initial epithelial activation. To change the disease trajectory, it is crucial to understand the mechanisms in the epithelium that are switched on early in smokers. One such mechanism we believe is the process of epithelial to mesenchymal transition. This article highlights the importance of this profound epithelial cell plasticity in COPD and also its regulation. We consider that understanding early changes in COPD will open new windows for therapy.

Keywords: EGFR; HuR; MMP; TGFβ; cancer; epithelial-to-mesenchymal transition, EMT; fibrosis; inflammation

Conflict of interest statement

SSS is supported by Clifford Craig Foundation Launceston General Hospital, Rebecca L. Cooper Medical Research Foundation, Cancer Council Tasmania, and Thoracic Society of Australia & New Zealand (TSAN

References

  1. Am J Respir Crit Care Med. 2017 Jul 15;196(2):172-185 - PubMed
  2. Int J Chron Obstruct Pulmon Dis. 2014 May 27;9:533-42 - PubMed
  3. Respirology. 2017 Jan;22(1):133-140 - PubMed
  4. Respir Res. 2013 Jun 28;14:67 - PubMed
  5. Proc Am Thorac Soc. 2006 Nov;3(8):726-33 - PubMed
  6. Respir Res. 2011 Jun 09;12:76 - PubMed
  7. Respirology. 2017 Aug;22(6):1125-1132 - PubMed
  8. Thorax. 2013 Aug;68(8):783-4 - PubMed
  9. Mol Cell. 2005 Sep 16;19(6):777-89 - PubMed
  10. Int J Chron Obstruct Pulmon Dis. 2017 Sep 07;12:2677-2679 - PubMed
  11. Eur Respir J. 2015 May;45(5):1258-72 - PubMed
  12. Drugs. 2018 Nov;78(16):1717-1740 - PubMed
  13. Respir Res. 2016 Feb 22;17:20 - PubMed
  14. Sci Rep. 2017 Oct 17;7(1):13392 - PubMed
  15. Biomed J. 2017 Dec;40(6):305-312 - PubMed
  16. Am J Respir Crit Care Med. 2017 Aug 1;196(3):393-394 - PubMed
  17. Clin Transl Med. 2014 Dec;3(1):33 - PubMed
  18. Cell Biol Int. 2017 Sep;41(9):960-968 - PubMed
  19. Ann Am Thorac Soc. 2014 Dec;11 Suppl 5:S252-8 - PubMed
  20. Respir Res. 2018 Jun 4;19(1):109 - PubMed
  21. Biomedicine (Taipei). 2016 Mar;6(1):5 - PubMed
  22. Chest. 1993 May;103(5):1429-32 - PubMed
  23. Lab Invest. 2018 Sep;98(9):1159-1169 - PubMed
  24. J Pathol. 2016 Dec;240(4):397-409 - PubMed
  25. Lung Cancer. 2018 Aug;122:44-53 - PubMed
  26. Expert Rev Respir Med. 2014 Oct;8(5):547-59 - PubMed
  27. Lancet Respir Med. 2018 Aug;6(8):591-602 - PubMed
  28. Pulm Pharmacol Ther. 2014 Dec;29(2):121-8 - PubMed
  29. Med Oncol. 2017 Mar;34(3):45 - PubMed
  30. Front Immunol. 2015 Nov 25;6:602 - PubMed
  31. J Mol Med (Berl). 2008 May;86(5):507-22 - PubMed
  32. Clin Immunol. 2014 Mar;151(1):1-15 - PubMed
  33. Respir Investig. 2017 Mar;55(2):104-113 - PubMed
  34. Eur Respir J. 2018 Jan 31;51(2): - PubMed
  35. J Biol Chem. 2012 Mar 2;287(10):7026-38 - PubMed
  36. J Natl Cancer Inst. 2001 Jul 18;93(14):1081-8 - PubMed
  37. Thorax. 2013 May;68(5):410-20 - PubMed
  38. Thorax. 2017 Aug;72(8):746-759 - PubMed
  39. Am J Respir Crit Care Med. 2011 Mar 15;183(6):723-33 - PubMed
  40. Clin Sci (Lond). 2018 Feb 8;132(3):375-379 - PubMed
  41. Am J Respir Crit Care Med. 2018 Jan 1;197(1):56-65 - PubMed
  42. Biol Chem. 2004 Jul;385(7):649-53 - PubMed
  43. Expert Rev Respir Med. 2017 Oct;11(10):827-839 - PubMed
  44. Eur Respir J. 2006 Sep;28(3):533-41 - PubMed
  45. Lab Invest. 2019 Feb;99(2):150-157 - PubMed
  46. Eur Respir J. 2016 Aug;48(2):359-69 - PubMed
  47. Eur Respir J. 2016 Aug;48(2):504-15 - PubMed
  48. Int J Biochem Cell Biol. 2015 Nov;68:59-69 - PubMed
  49. Int J Chron Obstruct Pulmon Dis. 2016 Sep 22;11:2359-2367 - PubMed
  50. Ann Am Thorac Soc. 2017 Sep;14(9):1491-1492 - PubMed
  51. J Biol Chem. 2016 Jan 1;291(1):291-302 - PubMed
  52. Cell Signal. 2016 May;28(5):498-505 - PubMed
  53. Am J Respir Crit Care Med. 1995 Nov;152(5 Pt 2):S77-121 - PubMed
  54. Am J Respir Cell Mol Biol. 2018 Feb;58(2):157-169 - PubMed
  55. Sci Rep. 2017 Sep 7;7(1):10832 - PubMed
  56. Respirology. 2010 Aug;15(6):930-8 - PubMed
  57. PLoS One. 2012;7(6):e39736 - PubMed
  58. Thorax. 2007 Nov;62(11):932-7 - PubMed
  59. Eur Respir J. 2016 Aug;48(2):301-4 - PubMed
  60. Pulm Pharmacol Ther. 2014 Aug;28(2):138-48 - PubMed
  61. Cell Mol Life Sci. 2011 Mar;68(5):877-92 - PubMed
  62. Eur Respir J. 2017 Jun 15;49(6): - PubMed
  63. Biochem Biophys Res Commun. 2015 Jan 30;457(1):65-70 - PubMed
  64. Am J Respir Crit Care Med. 2018 Jun 15;197(12):1644-1645 - PubMed
  65. PLoS One. 2011;6(9):e25450 - PubMed
  66. Am J Physiol Lung Cell Mol Physiol. 2013 Feb 15;304(4):L199-209 - PubMed
  67. Int J Chron Obstruct Pulmon Dis. 2015 Aug 04;10:1515-24 - PubMed
  68. World J Clin Cases. 2015 May 16;3(5):393-404 - PubMed
  69. Am J Respir Crit Care Med. 2019 Jan 15;199(2):250-251 - PubMed
  70. Biomarkers. 2018 Nov;23(7):709-711 - PubMed
  71. Respir Res. 2011 Oct 05;12:130 - PubMed
  72. Zhonghua Jie He He Hu Xi Za Zhi. 2017 Jul 12;40(7):515-519 - PubMed
  73. Respiration. 2011;81(5):353-8 - PubMed
  74. Respir Res. 2010 Jul 30;11:105 - PubMed
  75. Respirology. 2017 Jan;22(1):61-70 - PubMed
  76. Am J Respir Cell Mol Biol. 2015 Jun;52(6):653-62 - PubMed
  77. J Clin Invest. 2012 Jan;122(1):48-61 - PubMed
  78. Dev Dyn. 2018 Mar;247(3):346-358 - PubMed
  79. Nat Commun. 2012 Mar 13;3:735 - PubMed
  80. Am J Respir Crit Care Med. 2016 Mar 15;193(6):642-51 - PubMed
  81. EBioMedicine. 2015 Oct 17;2(11):1578-9 - PubMed

MeSH terms

Publication Types