open access
Vol 69, No 3 (2018)
Original paper
Submitted: 2017-10-20
Accepted: 2017-12-22
Published online: 2018-05-08
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Study on the relationship between the methylation of the MMP-9 gene promoter region and diabetic nephropathy
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open access
Vol 69, No 3 (2018)
Original Paper
Submitted: 2017-10-20
Accepted: 2017-12-22
Published online: 2018-05-08
Abstract
Objective: This study aims to explore the relationship between the methylation of matrix metalloproteinase (MMP)-9 gene promoter region and diabetic nephropathy (DN) through the detection of the methylation level of MMP-9 gene promoter region in the peripheral blood of patients with DN in different periods and serum MMP-9 concentration. Methods: The methylation level of the MMP-9 gene promoter region was detected by methylation-specific polymerase chain reaction (MSP), and the content of MMP-9 in serum was determined by enzyme-linked immunosorbent assay (ELISA). Results: Results of the statistical analysis revealed that serum MMP-9 protein expression levels gradually increased in patients in the simple diabetic group, early diabetic nephropathy group and clinical diabetic nephropathy group, compared with the control group; and the difference was statistically significant (P < 0.05). Compared with the control group, the methylation levels of MMP-9 gene promoter regions gradually decreased in patients in the simple diabetic group, early diabetic nephropathy group, and clinical diabetic nephropathy group; and the difference was statistically significant (P < 0.05). Furthermore, correlation analysis results indicated that the demethylation levels of the MMP-9 gene promoter region was positively correlated with serum protein levels, urinary albumin to creatinine ratio (UACR), urea and creatinine; and was negatively correlated with GFR. Conclusion: The demethylation of the MMP-9 gene promoter region may be involved in the occurrence and development of diabetic nephropathy by regulating the expression of MMP-9 protein in serum.
Abstract
Objective: This study aims to explore the relationship between the methylation of matrix metalloproteinase (MMP)-9 gene promoter region and diabetic nephropathy (DN) through the detection of the methylation level of MMP-9 gene promoter region in the peripheral blood of patients with DN in different periods and serum MMP-9 concentration. Methods: The methylation level of the MMP-9 gene promoter region was detected by methylation-specific polymerase chain reaction (MSP), and the content of MMP-9 in serum was determined by enzyme-linked immunosorbent assay (ELISA). Results: Results of the statistical analysis revealed that serum MMP-9 protein expression levels gradually increased in patients in the simple diabetic group, early diabetic nephropathy group and clinical diabetic nephropathy group, compared with the control group; and the difference was statistically significant (P < 0.05). Compared with the control group, the methylation levels of MMP-9 gene promoter regions gradually decreased in patients in the simple diabetic group, early diabetic nephropathy group, and clinical diabetic nephropathy group; and the difference was statistically significant (P < 0.05). Furthermore, correlation analysis results indicated that the demethylation levels of the MMP-9 gene promoter region was positively correlated with serum protein levels, urinary albumin to creatinine ratio (UACR), urea and creatinine; and was negatively correlated with GFR. Conclusion: The demethylation of the MMP-9 gene promoter region may be involved in the occurrence and development of diabetic nephropathy by regulating the expression of MMP-9 protein in serum.
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Keywords
diabetic nephropathy, matrix metalloproteinase-9, DNAmethylation
About this articleTitle
Study on the relationship between the methylation of the MMP-9 gene promoter region and diabetic nephropathy
Journal
Issue
Article type
Original paper
Pages
269-275
Published online
2018-05-08
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2752
Article views/downloads
1442
DOI
Pubmed
Bibliographic record
Endokrynol Pol 2018;69(3):269-275.
Keywords
diabetic nephropathy
matrix metalloproteinase-9
DNAmethylation
Authors
Xiao-Hui Yang
Shi-Ya Feng
Yang Yu
Zhou Liang
References (15)- Wu KI, Schmid-Schönbein GW. Nuclear factor kappa B and matrix metalloproteinase induced receptor cleavage in the spontaneously hypertensive rat. Hypertension. 2011; 57(2): 261–268.
- Raffetto JD, Khalil RA. Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease. Biochem Pharmacol. 2008; 75(2): 346–359.
- Chicoine E, Estève PO, Robledo O, et al. Evidence for the role of promoter methylation in the regulation of MMP-9 gene expression. Biochem Biophys Res Commun. 2002; 297(4): 765–772.
- Roach HI, Yamada N, Cheung KSC, et al. Association between the abnormal expression of matrix-degrading enzymes by human osteoarthritic chondrocytes and demethylation of specific CpG sites in the promoter regions. Arthritis Rheum. 2005; 52(10): 3110–3124.
- Betz B, Conway BR. Recent advances in animal models of diabetic nephropathy. Nephron Exp Nephrol. 2014; 126(4): 191–195.
- Wren JD, Garner HR. Data-mining analysis suggests an epigenetic pathogenesis for type 2 diabetes. J Biomed Biotechnol. 2005; 2005(2): 104–112.
- Keating ST, El-Osta A. Epigenetic changes in diabetes. Clin Genet. 2013; 84(1): 1–10.
- Sidaway P. Diabetes: Epigenetic changes lead to impaired wound healing in patients with T2DM. Nat Rev Endocrinol. 2015; 11(2): 65.
- Sapienza C, Lee J, Powell J, et al. DNA methylation profiling identifies epigenetic differences between diabetes patients with ESRD and diabetes patients without nephropathy. Epigenetics. 2011; 6(1): 20–28.
- McLennan SV, Kelly DJ, Cox AJ, et al. Decreased matrix degradation in diabetic nephropathy: effects of ACE inhibition on the expression and activities of matrix metalloproteinases. Diabetologia. 2002; 45(2): 268–275.
- Tashiro K, Koyanagi I, Ohara I, et al. Levels of urinary matrix metalloproteinase-9 (MMP-9) and renal injuries in patients with type 2 diabetic nephropathy. J Clin Lab Anal. 2004; 18(3): 206–210.
- Li SY, Huang PH, Yang AH, et al. Matrix metalloproteinase-9 deficiency attenuates diabetic nephropathy by modulation of podocyte functions and dedifferentiation. Kidney Int. 2014; 86(2): 358–369.
- Campos K, Gomes CC, Farias LC, et al. DNA Methylation of MMP9 Is Associated with High Levels of MMP-9 Messenger RNA in Periapical Inflammatory Lesions. J Endod. 2016; 42(1): 127–130.
- Sato N, Maehara N, Su GH, et al. Effects of 5-aza-2'-deoxycytidine on matrix metalloproteinase expression and pancreatic cancer cell invasiveness. J Natl Cancer Inst. 2003; 95(4): 327–330.
- Chicoine E, Estève PO, Robledo O, et al. Evidence for the role of promoter methylation in the regulation of MMP-9 gene expression. Biochem Biophys Res Commun. 2002; 297(4): 765–772.
