DEVELOPMENT OF A STUDY MODEL FOR DIABETIC NEPHROPATHY TROUGHOUT OVEREXPRESSION OF ALDOSE REDUCTASE
Diabetes has deleterious effects on the most different organs, and one origin of these effects is caused by the accumulation of glucose in cells due to hyperglycemia. Some of the main organs affected by this event are the kidneys, which gradually lose their function and may progress to organ failure. One of the central pathways for kidney cell impairment is the polyol pathway, which transforms excess cellular glucose into sorbitol and subsequently to fructose. The molecules involved in this process, when deregulated, can cause cell dysfunction and serve as a stimulus for other pathways that add to this deleterious effect, having a close relationship with osmotic and oxidative stress processes. The aim of the study was to analyze cellular modifications caused in transformed HEK-293 (HEK-TG), which have renal characteristics, from the overexpression of aldose reductase Akr1b3, using the TET-On system as a mechanism for inducing the genes of interest. HEK-TG cells were stimulated to activate the overexpression of the gene, being qualitatively analyzed in terms of morphology and expression of genes related to osmotic stress resulting from the stimulation of sorbitol production. Morphological analysis indicated rare cells with increased volume and visible cellular changes, but not enough for these changes to be significant. The analyzes on the expression of genes related to osmotic stress did not change in the group with promoter activation compared to the control groups. It can be concluded that there were no significant osmotic changes in the cells during the studied period, however changes in shorter periods of time and also changes arising from oxidative stress cannot be ruled out.