Skip to main content
Log in

Comparative mRNA and microRNA expression profiling of methylglyoxal-exposed human endothelial cells

  • Original Article
  • Published:
BioChip Journal Aims and scope Submit manuscript

Abstract

Methylglyoxal (MG) is a highly toxic compound that contributes to the formation of advanced glycation end products (AGEs). MG is detected at high concentration in plasma of diabetic patients and is involved in the pathogenesis of several diabetic macro- and microvascular complications, such as atherosclerosis, retinopathy, nephropathy and hypertension. MicroRNAs (miRNAs) play a critical role in the negative regulation of genes in many biologic processes. They are also known to post-transcriptionally regulate gene expression involved in cellular responses to toxicants. In this study, we investigated whether miRNAs play a role in the regulation of gene expressions in human umbilical vein endothelial cells (HUVECs) after the treatment with MG. We performed pair-wise correlation analysis, acquired altered expression levels of 274 miRNAs and 686 mRNA, and observed their anti-correlations. Genes associated with diabetic vascular disease were sorted from miRNA-correlated genes, and Gene Ontology (GO) enrichment analysis on the differential expression of selected genes was carried out. Our results revealed the relationship between miRNAs and mRNA in MG-exposed endothelial cells using the expression profiling.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Brandt, R.B. & Siegel, S.A. Methylglyoxal production in human blood. Ciba Found. Symp. 67, 211–223 (1978).

    Google Scholar 

  2. Westwood, M.E., McLellan, A.C. & Thornalley, P.J. Receptor-mediated endocytic uptake of methylglyoxal-modified serum albumin. Competition with advanced glycation end product-modified serum albumin at the advanced glycation end product receptor. J. Biol. Chem. 269, 32293–32298 (1994).

    CAS  Google Scholar 

  3. Thornalley, P.J. Pharmacology of methylglyoxal: formation, modification of proteins and nucleic acids, and enzymatic detoxification-a role in pathogenesis and antiproliferative chemotherapy. Gen. Pharmacol. 27, 565–573 (1996).

    Article  CAS  Google Scholar 

  4. Vander Jagt, D.L. Methylglyoxal, diabetes mellitus and diabetic complications. Drug Metab. Drug Interact. 23, 93–124 (2008).

    Article  Google Scholar 

  5. Sejersen, H. & Rattan, S.I.S. Dicarbonyl-induced accelerated aging in vitro in human skin fibroblasts. Biogerontology 10, 203–211 (2009).

    Article  CAS  Google Scholar 

  6. Choudhary, D., Chandra, D. & Kale, R.K. Influence of methylglyoxal on antioxidant enzymes and oxidative damage. Toxicol. Lett. 93, 141–152 (1997).

    Article  CAS  Google Scholar 

  7. Lee, S.E. et al. Methylglyoxal-mediated alteration of gene expression in human endothelial cells. BioChip J. 5, 220–228 (2011).

    Article  CAS  Google Scholar 

  8. Wang, H., Liu, J. & Wu, L. Methylglyoxal-induced mitochondrial dysfunction in vascular smooth muscle cells. Biochem. Pharmacol. 77, 1709–1716 (2009).

    Article  CAS  Google Scholar 

  9. Cantero, A.V. et al. Methylglyoxal induces advanced glycation end product (AGEs) formation and dysfunction of PDGF receptor-beta: implications for diabetic atherosclerosis. FASEB J. 21, 3096–3106 (2007).

    Article  CAS  Google Scholar 

  10. Jeong, S.I. et al. Effect of alpha,beta-unsaturated aldehydes on endothelial cell growth in bacterial cellulose for vascular tissue engineering. Mol. Cell. Toxicol. 8, 119–126 (2012).

    Article  CAS  Google Scholar 

  11. Park, Y.S. et al. Acrolein induces cyclooxygenase-2 and prostaglandin production in human umbilical vein endothelial cells-Roles of p38 MAP kinase. Arterioscler. Thromb. Vasc. Biol. 27, 1319–1325 (2007).

    Article  CAS  Google Scholar 

  12. Yang, H. et al. An integrated analysis of microRNA and mRNA expression in salvianolic acid B-treated human umbilical vein endothelial cells. Mol. Cell. Toxicol. 9, 1–7 (2013).

    Article  CAS  Google Scholar 

  13. Asgeirsdottir, S.A. et al. MicroRNA-126 contributes to renal microvascular heterogeneity of VCAM-1 protein expression in acute inflammation. Am. J. Physiol. Renal. Physiol. 302, 1630–1639 (2012).

    Article  Google Scholar 

  14. Lema, C. & Cunningham, M.J. MicroRNAs and their implications in toxicological research. Toxicol. Lett. 198, 100–105 (2010).

    Article  CAS  Google Scholar 

  15. Paul, S. et al. Impact of miRNA deregulation on mRNA expression profiles in response to environmental toxicant, nonylphenol. Mol. Cell. Toxicol. 7, 259–269 (2011).

    Article  CAS  Google Scholar 

  16. Sun, X. et al. MicroRNA-181b regulates NF-kappaB-mediated vascular inflammation. J. Clin. Invest. 122, 1973–1990 (2012).

    CAS  Google Scholar 

  17. Caruso, P. et al. A Role for miR-145 in Pulmonary Arterial Hypertension. Circ. Res. 111, 290–300 (2012).

    Article  CAS  Google Scholar 

  18. Fish, J.E. A primer on the role of MicroRNAs in endothelial biology and vascular disease. Semin. Nephrol. 32, 167–175 (2012).

    Article  CAS  Google Scholar 

  19. Kim, J.H. Cardiovascular diseases and panax ginseng: a review on molecular mechanisms and medical applications. J. Ginseng Res. 36, 16–26 (2012).

    Article  CAS  Google Scholar 

  20. Calles-Escandon, J. & Cipolla, M. Diabetes and endothelial dysfunction: a clinical perspective. Endocr. Rev. 22, 36–52 (2001).

    Article  CAS  Google Scholar 

  21. Phillips, S.A., Mirrlees, D. & Thornalley, P.J. Modification of the glyoxalase system in streptozotocin-induced diabetic rats. Effect of the aldose reductase inhibitor Statil. Biochem. Pharmacol. 46, 805–811 (1993).

    Article  CAS  Google Scholar 

  22. Han, Y. et al. Plasma methylglyoxal and glyoxal are elevated and related to early membrane alteration in young, complication-free patients with Type 1 diabetes. Mol. Cell. Biochem. 305, 123–131 (2007).

    Article  CAS  Google Scholar 

  23. Ogawa, S. et al. Methylglyoxal is a predictor in type 2 diabetic patients of intima-media thickening and elevation of blood pressure. Hypertension 56, 471–476 (2010).

    Article  CAS  Google Scholar 

  24. Forbes, J.M. et al. Advanced glycation end product interventions reduce diabetes-accelerated atherosclerosis. Diabetes 53, 1813–1823 (2004).

    Article  CAS  Google Scholar 

  25. Vasdev, S. & Stuckless, J. Role of methylglyoxal in essential hypertension. Int. J. Angiol. 19, e58–65 (2010).

    Article  Google Scholar 

  26. Zou, C., Wang, S., Huang, F. & Zhang, Y.A. Advanced glycation end products and ultrastructural changes in corneas of long-term streptozotocin-induced diabetic monkeys. Cornea 31, 1455–1459 (2012).

    Article  Google Scholar 

  27. Srikanth, V. et al. Methylglyoxal, cognitive function and cerebral atrophy in older people. J. Gerontol. A. Biol. Sci. Med. Sci. 68, 68–73 (2012).

    Article  Google Scholar 

  28. Lee, S.E. et al. MicroRNA and gene expression analysis of melatonin-exposed human breast cancer cell lines indicating involvement of the anticancer effect. J. Pineal. Res. 51, 345–352 (2011).

    Article  CAS  Google Scholar 

  29. Mirnics, K. & Pevsner, J. Progress in the use of microarray technology to study the neurobiology of disease. Nature Neurosci. 7, 434–439 (2004).

    Article  CAS  Google Scholar 

  30. Fekete, V. et al. Effect of type 2 diabetes on the gene expression pattern of rat hearts: a DNA microarray study. Cardiovasc. Res. 87, S116–S116 (2010).

    Google Scholar 

  31. Lee, S.E. et al. Differentially-expressed genes related to atherosclerosis in acrolein-stimulated human umbilical vein endothelial cells. BioChip J. 4, 264–271 (2010).

    Article  CAS  Google Scholar 

  32. Ziyadeh, F.N. The extracellular matrix in diabetic nephropathy. Am J. Kidney Dis. 22, 736–744 (1993).

    CAS  Google Scholar 

  33. Ho, C. et al. Methylglyoxal-induced Fibronectin gene expression through Ras-mediated NADPH oxidase activation in renal mesangial cells. Nephrology 12, 348–356 (2007).

    Article  CAS  Google Scholar 

  34. Golej, J., Hoeger, H., Radner, W., Unfried, G. & Lubec, G. Oral administration of methylglyoxal leads to kidney collagen accumulation in the mouse. Life Sci. 63, 801–807 (1998).

    Article  CAS  Google Scholar 

  35. Staimer, N., Nguyen, T.B., Nizkorodov, S.A. & Delfino, R.J. Glutathione peroxidase inhibitory assay for electrophilic pollutants in diesel exhaust and tobacco smoke. Anal. Bioanal. Chem. 403, 431–441 (2012).

    Article  CAS  Google Scholar 

  36. Park, Y.S. et al. Identification of the binding site of methylglyoxal on glutathione peroxidase: methylglyoxal inhibits glutathione peroxidase activity via binding to glutathione binding sites Arg 184 and 185. Free Radic. Res. 37, 205–211 (2003).

    Article  CAS  Google Scholar 

  37. Yang, H. et al. Up-regulation of Heme Oxygenase-1 by Korean Red Ginseng Water Extract as a Cytoprotective Effect in Human Endothelial Cells. J. Ginseng Res. 35, 352–359 (2011).

    Article  CAS  Google Scholar 

  38. Yang, H. et al. Expression profile analysis of human umbilical vein endothelial cells treated with salvianolic acid B from Salvia miltiorrhiza. BioChip J. 5, 47–55 (2011).

    Article  Google Scholar 

  39. Lee, S.E. et al. Induction of Heme Oxygenase-1 Inhibits Cell Death in Crotonaldehyde-Stimulated HepG2 Cells via the PKC-delta-p38-Nrf2 Pathway. PLoS One 7, e41676 (2012).

    Article  CAS  Google Scholar 

  40. Lee, S.E. et al. Genome-wide profiling in melatonin-exposed human breast cancer cell lines identifies differentially methylated genes involved in the anticancer effect of melatonin. J. Pineal. Res. 54, 80–88 (2013).

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yong Seek Park.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yang, H., Kim, GD., Park, H.R. et al. Comparative mRNA and microRNA expression profiling of methylglyoxal-exposed human endothelial cells. BioChip J 7, 143–150 (2013). https://doi.org/10.1007/s13206-013-7207-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13206-013-7207-7

Keywords

Navigation