Investigation of transglutaminase 2 and C-peptide functions in diabetic nephropathy
Project no. 20038 · Status: Kapanmış (Yayın bekleniyor) · 2019
Summary
Diabetic nephropathy (DN), which is one of the most important microvascular complications of Diabetes Mellitus, affects nearly 45 % of people with diabetes and cause end-stage kidney disease. Current treatment approaches are insufficient on microvascular damage. Therefore, in recent years, besides the glycemic control, studies on the treatment of cell damage due to high glucose have accelerated. In this study, it was aimed to investigate the possible functions of transglutaminase 2 (TG2) and C-peptide in human renal tubular epithelial cells (HK-2) which exposed to high glucose to realize an in vitro diabetic nephropathy model. For this purpose, TG2 activity and expression, intracellular reactive oxygen species (ROS) and calcium levels, nitrite content, apoptosis related parameters and cell viability were examined under the specified conditions. Then, the effect of C-peptide treatment on these parameters was detected. As a result of the studies; increased TG2 activity and expression were determined in high glucose-induced HK-2 cells. In addition, increased intracellular ROS, calcium, nitrite levels and apoptosis related parameters were detected. When TG2 activity was inhibited, intracellular calcium and ROS levels and apoptosis markers decreased. In addition, an increase in expression of anti-apoptotic proteins and an increase in cell viability were observed. On the other hand, Cpeptide treatment was found to cause a decrease in TG2 activity and expression. However, intracellular calcium level, ROS level, and apoptosis related markers were decreased, whereas expression of anti-apoptotic proteins and cell viability were increased, in the presence of Cpeptide. In conclusion; increased TG2 activity and expression in HK-2 cells as a result of high glucose induction suggests that this enzyme plays a role in the pathogenesis of DN. The decrease in TG2 activity and increase in antiapoptotic proteins in HK-2 cells as a result of C-peptide treatment may be attributed to the protective effect of C-peptide. These results suggest that Cpeptide is a promising molecule in the treatment of diabetic nephropathy.