title: Inhibition to DRP1 translocation can mitigate p38 MAPK-signaling pathway activation in GMC induced by hyperglycemia.
abstract: 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.
authors: a Division of Nephrology , West China Hospital of Sichuan University , Chengdu , Sichuan , China.
authors: LieMei
authors: L
authors: Zhang
authors: Ling
authors: L
authors: Ji
authors: XiaoHong
authors: X
authors: Tang
authors: XiaoLei
authors: X
authors: Chen
authors: Zi
authors: Z
authors: Li
authors: XuHua
authors: X
authors: Mi
authors: LiChuan
authors: L
authors: Yang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000473:pathology*; D034281:Dynamins / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006943:Hyperglycemia; D050527:Mesangial Cells / Q000187:drug effects*; D008928:Mitochondria / Q000648:ultrastructure*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D024141:Collagen Type IV; D048051:p38 Mitogen-Activated Protein Kinases; C519851:Dnm1l protein, rat; D034281:Dynamins; D005947:Glucose
keywords: DRP1; Diabetic nephropathy; mitochondria