Elevated glucose represses lysosomal and mTOR-related genes in renal epithelial cells composed of progenitor CD133+ cells.

Abstract

Hyperglycemia is one of the major health concern in many parts of the world. One of the serious complications of high glucose levels is diabetic nephropathy. The preliminary microarray study performed on primary human renal tubular epithelial (hRTE) cells exposed to high glucose levels showed a significant downregulation of mTOR as well as its associated genes as well as lysosomal genes. Based on this preliminary data, the expression of various lysosomal genes as well as mTOR and its associated genes were analyzed in hRTE cells exposed to 5.5, 7.5, 11 and 16 mM glucose. The results validated the microarray analysis, which showed a significant decrease in the mRNA as well as protein expression of the selected genes as the concentration of glucose increased. Co-localization of lysosomal marker, LAMP1 with mTOR showed lower expression of mTOR as the glucose concentration increased, suggesting decrease in mTOR activity. Although the mechanism by which glucose affects the regulation of lysosomal genes is not well known, our results suggest that high levels of glucose may lead to decrease in mTOR expression causing the cells to enter an anabolic state with subsequent downregulation of lysosomal genes.