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Role of epigenetic mechanisms in the development of chronic complications of diabetes

Wegner, Malgorzata and Neddermann, Daniel and Piorunska-Stolzmann, Maria and Jagodzinski, Pawel (2014) Role of epigenetic mechanisms in the development of chronic complications of diabetes. Diabetes Research and Clinical Practice, 105 (2). pp. 164-175. ISSN 0168-8227

Abstract

Genetic factors cannot independently explain the causes of chronic complications associated
with diabetes mellitus (DM). It indicates that epigenetic regulation of gene expression including posttranslational histone modifications (PTHMs), DNA methylation and microRNA (miRNA)-regulation of mRNA translation could play a crucial role in the development of chronic complications.
Hyperglycemia (HG) induces an abnormal action of PTHMs and DNA methyltransferases as well as
alters the levels of numerous miRNAs in endothelial cells, vascular smooth muscle cells,
cardiomyocytes, retina, and renal cells. These epigenetic abnormalities result in changes in the
expression of numerous genes contributing to development of chronic inflammation, impaired
clearance of reactive oxygen species (ROS), endothelial cells dysfunction and/or accumulation of
extracellular matrix in the kidney, causing development of retinopathy, nephropathy or
cardiomyopathy. Some of epigenetic modifications, as PTHMs and DNA methylation, become over time irreversible. These epigenetic changes could explain the "metabolic memory", a phenomenon related to the harmful effect of HG which gives cells a constant pathogenic character causing development of chronic complications even after normoglycemia is achieved. In conclusion, the knowledge summarized in this review suggests that the treatment of chronic complications should focus on erasing metabolic memory by targeting chromatin modification enzymes and by restoring miRNAs levels.

Item Type: Article
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Keywords: diabetes, chronic complications, metabolic memory, epigenetic
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Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13
URI: https://oak.novartis.com/id/eprint/11067

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