Kruppel-Like Transcription Factor-4 Gene Expression and DNA Methylation Status in Type 2 Diabetes and Diabetic Nephropathy Patients

Arch Med Res. 2019 Apr;50(3):91-97. doi: 10.1016/j.arcmed.2019.05.012. Epub 2019 Jul 24.

Abstract

Background/aim: Diabetic nephropathy (DN) is one of the most serious microvascular complications in diabetic patients. The kruppel-like transcription factor-4 (KLF-4) affects the expression of genes involved in the pathogenesis of DN. The present study aims to identify the KLF-4 expression and DNA methylation (DNAMe) status in patients with type-2 diabetes (T2D) and DN and to reveal the contribution of the KLF-4 to the development of DN.

Material and methods: The cohort study was performed with blood samples from 120 individuals; T2D group (n = 40), DN group (n = 40) and control group (n = 40). The expression level of the KLF-4 gene was analyzed using the real-time polymerase chain reaction (qRT-PCR) and the methylation profile detected using the methylation-specific PCR (MS-PCR) technique.

Results: According to our findings, KLF-4 mRNA expression in the T2D group was 1.60 fold lower than in the control group (p = 0.001). In the DN group, the expression of KLF-4 mRNA was 2.92-fold less than that of the T2D group (p = 0.001). There was no significant alteration in the DNAMe status among the groups.

Conclusion: Our findings showed that regardless of the DNAMe status, KLF-4 gene expression may play a role in the development of T2D and DN. This suggests that the KLF-4 gene may be the target gene in understanding the mechanism of nephropathy, which is the most important complication of diabetes, and planning nephropathy-related treatments, but the data should be supported with more studies.

Keywords: DNA methylation; Diabetic nephropathy; Epigenetics; Kruppel-like transcription factor-4; Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • DNA Methylation / genetics*
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetic Nephropathies / genetics*
  • Diabetic Nephropathies / metabolism
  • Female
  • Gene Expression
  • Humans
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / biosynthesis
  • Kruppel-Like Transcription Factors / genetics*
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger / metabolism

Substances

  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • RNA, Messenger