The renal expression of epigenetic biomarkers for diabetic nephropathy

Abstract

Chronic kidney disease (CKD) is one of the most common complications in patients with diabetes. Identification of diabetic patients with high risk for CKD progression has been challenging due to various limitations of traditional diagnostic methods. Epigenetic modifications, particularly DNA methylation, have recently emerged as alternative predicting factors for diabetic nephropathy. Despite strong evidence of correlation, the mechanisms that link epigenetic changes in blood/monocytes with renal physiology are yet to be investigated. As such, it is important to examine the renal expression of these differentially methylated genes in diabetic individuals with and without CKD. Using an animal model of Type 2 diabetes (T2D) and biopsy/nephrectomy samples from patients with T2D without and with CKD, we demonstrated that CUE domain containing 1 (cuedc1), microtubule-associated protein 7 (map7), LIM Homeobox 6 (lhx6) and Thioredoxin Interacting Protein (Txnip) were downregulated in the kidneys of T2D animals and patients without CKD. Strikingly, the regulation of cuedc1, map7 and txnip were significantly reversed in the presence of kidney dysfunction and fibrosis. The expression of Protein Kinase C Epsilon (prkce) was also significantly higher in T2D patients with CKD compared to the control group. Both txnip and prkce have been shown previously to be involved in the induction of diabetic nephropathy. These data provide evidence to support the relevance of epigenetic biomarkers in blood with renal pathophysiology in T2D.