Diabetic nephropathy (DN) is a serious complication of diabetes with a poorly defined etiology and limited treatment options. Early intervention is a key to preventing the progression of DN. Dynamin-related protein 1 (DRP1) regulates mitochondrial morphology by promoting its fission and is involved in the pathogenesis of numerous diseases. Furthermore, DRP1 is also closely associated with the development of diabetes, but its functional role in DN remains unknown. This study investigated the effect of DRP1 on early stage of DN. DRP1 expression has increased significantly in glomerular mesangial cell (GMC), which is cultivated in high glucose (HG). Ultra-microstructural changes of nephrons, expression of collagen IV and phosph-p38, ROS production, and mitochondrial function were evaluated and, at the same time, were compared with glomerular mesangial cell (GMC) cultured in normal-glucose (NG), mannitol, and a medium with mitochondrial division inhibitor 1 (Midivi-1). Endogenous DRP1 expression increased in DN. Compared to the control groups ofNG and mannitol, overexpression of DRP1 destroyed pathological changes typical of the GMC, like accumulation of extracellular matrix, and an increase in mitochondria division. In addition, Overexpression of DRP1 promoted the activation of p38, the accumulation of ROS, mitochondrial dysfunction, and the synthesis of collagen IV, and all these changes are suppressed by Midivi-1. This study demonstrates that DRP1 overexpression can accelerate pathological changes in the GMC cultured in HG. Further studies are needed to clarify the underlying mechanism of this destructive function.
Keywords: DRP1; Diabetic nephropathy; mitochondria.