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02 22, 2018;8 (1): 3502.

Bronchial extracellular matrix from COPD patients induces altered gene expression in repopulated primary human bronchial epithelial cells.

Ulf Hedström, Oskar Hallgren, Lisa Öberg, Amy DeMicco, Outi Vaarala, Gunilla Westergren-Thorsson, Xiaohong Zhou
Author Information
  1. Ulf Hedström: Bioscience Regeneration Department, Respiratory, Inflammation and Autoimmunity, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
  2. Oskar Hallgren: Division of Lung Biology, Department of Experimental Medical Science, Lund University, Lund, Sweden.
  3. Lisa Öberg: Bioscience Immunity Department, Respiratory, Inflammation and Autoimmunity, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden. ORCID
  4. Amy DeMicco: Bioscience Regeneration Department, Respiratory, Inflammation and Autoimmunity, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
  5. Outi Vaarala: Bioscience Immunity Department, Respiratory, Inflammation and Autoimmunity, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
  6. Gunilla Westergren-Thorsson: Division of Lung Biology, Department of Experimental Medical Science, Lund University, Lund, Sweden.
  7. Xiaohong Zhou: Bioscience Regeneration Department, Respiratory, Inflammation and Autoimmunity, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden. Xiao-Hong.Zhou@astrazeneca.com.
PMID: 29472603 DOI: 10.1038/s41598-018-21727-w

Abstract

Chronic obstructive pulmonary disease (COPD) is a serious global health problem characterized by chronic airway inflammation, progressive airflow limitation and destruction of lung parenchyma. Remodeling of the bronchial airways in COPD includes changes in both the bronchial epithelium and the subepithelial extracellular matrix (ECM). To explore the impact of an aberrant ECM on epithelial cell phenotype in COPD we developed a new ex vivo model, in which normal human bronchial epithelial (NHBE) cells repopulate and differentiate on decellularized human bronchial scaffolds derived from COPD patients and healthy individuals. By using transcriptomics, we show that bronchial ECM from COPD patients induces differential gene expression in primary NHBE cells when compared to normal bronchial ECM. The gene expression profile indicated altered activity of upstream mediators associated with COPD pathophysiology, including hepatocyte growth factor, transforming growth factor beta 1 and platelet-derived growth factor B, which suggests that COPD-related changes in the bronchial ECM contribute to the defective regenerative ability in the airways of COPD patients.

References

  1. Matrix. 1991 Jun;11(3):177-83 [PMID: 1870448]
  2. Annu Rev Biochem. 2005;74:385-410 [PMID: 15952892]
  3. J Clin Invest. 1993 Aug;92 (2):632-7 [PMID: 7688761]
  4. Cell Physiol Biochem. 2017;41(6):2333-2349 [PMID: 28478450]
  5. Am J Physiol Lung Cell Mol Physiol. 2005 Apr;288(4):L641-7 [PMID: 15579628]
  6. Br J Pharmacol. 2003 Oct;140(4):595-610 [PMID: 14504135]
  7. Am J Respir Crit Care Med. 2008 Jul 1;178(1):81-8 [PMID: 18420966]
  8. Glycobiology. 2005 Dec;15(12):1277-85 [PMID: 16118286]
  9. Am J Respir Cell Mol Biol. 2008 Feb;38(2):209-17 [PMID: 17872495]
  10. PLoS Genet. 2013;9(2):e1003228 [PMID: 23459311]
  11. J Biol Chem. 2001 Jul 13;276(28):26077-83 [PMID: 11352916]
  12. J Biol Chem. 2013 May 31;288(22):15466-73 [PMID: 23580645]
  13. Cell Mol Life Sci. 2011 Mar;68(5):877-92 [PMID: 20820852]
  14. J Biol Chem. 2007 Sep 7;282(36):26418-30 [PMID: 17580303]
  15. J Cell Mol Med. 2015 Dec;19(12 ):2818-26 [PMID: 26416301]
  16. Proc Am Thorac Soc. 2009 Dec 1;6(7):607-13 [PMID: 19934357]
  17. Biomaterials. 2011 Apr;32(12):3233-43 [PMID: 21296410]
  18. J Biol Chem. 2010 Jun 4;285(23):17846-56 [PMID: 20375011]
  19. Am J Respir Crit Care Med. 2014 Sep 1;190(5):509-21 [PMID: 25078120]
  20. Am J Respir Crit Care Med. 2008 Aug 1;178(3):248-60 [PMID: 18467512]
  21. Am J Respir Cell Mol Biol. 2015 Mar;52(3):263-84 [PMID: 25303647]
  22. N Engl J Med. 2011 Oct 27;365(17 ):1567-75 [PMID: 22029978]
  23. Mol Pharmacol. 2007 Sep;72(3):769-79 [PMID: 17550984]
  24. PLoS One. 2013;8(2):e56587 [PMID: 23437179]
  25. J Biol Chem. 2006 Apr 14;281(15):10365-73 [PMID: 16455654]
  26. Mol Cell Biol. 2012 Mar;32(5):941-53 [PMID: 22203039]
  27. Biomaterials. 2014 Mar;35(10):3281-97 [PMID: 24461327]
  28. PLoS One. 2016 May 26;11(5):e0156009 [PMID: 27228128]
  29. Mol Cell Proteomics. 2012 Apr;11(4):M111.014647 [PMID: 22159717]
  30. Cancer Res. 2012 Apr 15;72(8):1943-52 [PMID: 22350411]
  31. Development. 1998 Apr;125(7):1315-24 [PMID: 9477330]
  32. PLoS Med. 2006 Nov;3(11):e442 [PMID: 17132052]
  33. J Biol Chem. 2008 Jan 18;283(3):1324-33 [PMID: 17981798]
  34. Lung. 2014 Feb;192(1):95-102 [PMID: 24153451]
  35. Eur Respir J. 2013 Nov;42(5):1345-56 [PMID: 23349442]
  36. Nat Methods. 2015 Apr;12(4):357-60 [PMID: 25751142]
  37. Eur Respir J. 2012 Dec;40(6):1362-73 [PMID: 22496324]
  38. Eur Respir J. 2008 Nov;32(5):1371-85 [PMID: 18978137]
  39. Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65 [PMID: 22878278]
  40. J Cell Physiol. 2001 Dec;189(3):266-74 [PMID: 11748584]
  41. Int J Biochem Cell Biol. 2017 Feb;83:27-38 [PMID: 27974233]
  42. Am J Clin Pathol. 2006 Nov;126(5):725-35 [PMID: 17111536]
  43. Biomaterials. 2011 Oct;32(29):7169-80 [PMID: 21724251]
  44. Bioinformatics. 2014 Feb 15;30(4):523-30 [PMID: 24336805]
  45. Proc Am Thorac Soc. 2012 Jul;9(3):111-6 [PMID: 22802283]
  46. Biomaterials. 2016 Nov;108:111-9 [PMID: 27622532]
  47. Stem Cells Transl Med. 2016 Oct;5(10 ):1307-1318 [PMID: 27388243]
  48. Respir Res. 2010 Nov 30;11:165 [PMID: 21118554]
  49. Bioinformatics. 2014 Apr 1;30(7):923-30 [PMID: 24227677]
  50. Chest. 2006 Oct;130(4):1102-8 [PMID: 17035444]
  51. J Lipid Res. 1999 Oct;40(10):1911-9 [PMID: 10508211]
  52. J Immunol. 2003 Apr 1;170(7):3679-87 [PMID: 12646633]
  53. Chest. 2014 Nov;146(5):1159-1165 [PMID: 24832895]
  54. Genome Biol. 2014;15(12):550 [PMID: 25516281]

MeSH Term

Bronchi
Connective Tissue Growth Factor
Epithelial Cells
Extracellular Matrix
Gene Expression Regulation
Hepatocyte Growth Factor
Humans
Lung
Primary Cell Culture
Proto-Oncogene Proteins c-sis
Pulmonary Disease, Chronic Obstructive
Respiratory Mucosa
Transcriptome
Transforming Growth Factor beta1

Chemicals

CCN2 protein, human
HGF protein, human
Proto-Oncogene Proteins c-sis
Transforming Growth Factor beta1
Connective Tissue Growth Factor
Hepatocyte Growth Factor
Journal Article Research Support, Non-U.S. Gov't

Links to CNCB-NGDC Resources

GEN: GEND000009 (RNA sequencing of human bronchial epithelial cell transcriptomes after repopulation and differentiation on bronchial scaffolds from COPD patients and healthy donors)

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