Epigenetic regulation of autophagy Related gene in diabetic nephropathy

Abstract

The natural history of DN is the development of persistent microalbuminuria (presence of albumin in the urine), which in some patients progresses to overt proteinuria followed by a gradual decline in glomerular filtration rate (GFR), eventually leading to renal failure However, not all patients fit the classical paradigm, as there is increasing evidence of renal impairment in the absence of albuminuria in some patients with DN. Autophagy, a highly regulated lysosomal pathway involved in the recycling of cytosol and the removal of superfluous or damaged organelles, is essential for the survival, differentiation, development and homeostasis of cells dysregulated autophagy has been suggested to play pathogenic roles in a variety of disease processes including cancer, neurodegeneration, diabetes, aging and heart disease. In diabetic nephropathy the expression of several microRNAs is dysregulated affecting several key proteins in various steps of autophagy, from proteins functioning in the upstream signaling pathways to the later stages of autophagic degradation contributing to the increased expression and accumulation of extracellular matrix proteins and increased pro-fibrotic signaling, ultimately resulting in renal fibrosis. In this regards, we evaluate the clinical utility of urinary MAPLC3 mRNA and WIPI2 mRNA expression as autophagy biomarkers and their epigenetic regulators miR-34a and miR-15a respectively as non-invasive biomarkers in diagnosis of diabetic nephropathy and to correlate their expression with different clinicopathological factors.