Monday, June 7, 2010


This month's Nature Review Nephrology dedicated an entire journal to the Concept of Diabetic Nephropathy.
There are many articles that are in the journal but a few highlights are worth mentioning.
1. The potential role of epigenetic mechanisms in diabetic nephropathy is intriguing. Epigenetics interact with genetic information and alter genetic expression and perhaps even cause human diseases. The Epigenetics concept is growing and even human behavior can change the epigenome. These epigenomes are sort of turn on and off switches of the genes.
The mention a concept of metabolic memory of renal cells and epigenomics in diabetes is new.  The question of whether transient hyperglycemia ( leading to a memory of that in the renal cells) due to glycosolated end products or AGE, can induce epigenetic modifications of gene expression  by affecting the methylation of particular parts of the genome is what is discussed in one of the articles. Metobolic memory is referred to as if the cells have seen prior hyperglycemia, they keep that memory and can later on return via epigenetic mechanism to lead to diabetic disease!

2. Another article discusses the concept of nuclear hormone receptors in diabetes.  Multiple nuclear hormone receptors have been linked with changes and leading to diabetic nephropahty in rat models. Some of the ones mentioned are PPARY, estrogen receptor, Vitamin D receptor, hepatocyte nuclear factor 4, farnesoid receptor, liver X receptor, and estrogen related receptors. All of these receptors in some shape of form have been linked to either renal fibrosis, proteinuria, mesangial expansion, lipid accumulation or macrophage infiltration( different stages of diabetic nephropathy)

3. The concept of RAGE or receptor of advanced glycalation endproducts is reviewed in one of the chapters.
RAGE is not only dominant player in diabetes but there have been papers regarding lupus, amyloidosis, ischemic renal injury as well. A simple way to conceptualize is the stimulus is likely elevated glucose that leads to activation of RAGE on the glomerular cells that leads to podocyte apoptosis and increase permeability; increased reactive oxygen species and increased TGF-B and fibrosis; increased CCL2 and hence increased inflammation via attraction of inflammatory cells and mesangial expansion.  All these phenomenon leading to increase damage and repair leading to the pathology we see in Diabetic Nephropathy.

The references:

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