title: Mesenchymal stem cells transplantation ameliorates glomerular injury in streptozotocin-induced diabetic nephropathy in rats via inhibiting oxidative stress.
abstract: OBJECTIVE
  Mesenchymal stem cells (MSCs) have been demonstrated to be protective in diabetic nephropathy (DN) by reducing albuminuria and attenuating glomerular injury. However, the mechanisms remain unclear. The aim of this study was to explore the effects of MSCs on oxidative stress in DN.
  
  
  METHODS
  Streptozotocin-induced diabetic rats received no treatment or treatment with MSCs (2×10(6), via tail vein) for two continuous weeks. Two other control groups received the antioxidant-probucol or insulin. Eight weeks after treatment, physical, biochemical, renal functional and morphological parameters were measured. Glomerular mesangial cells were cultured for the in vitro experiment.
  
  
  RESULTS
  Green fluorescent protein-labeled MSCs were only detected around the glomeruli and near vessels in the kidney. MSCs treatment dramatically reduced blood glucose, urinary albumin excretion, creatinine clearance and renal mass index. The glomerulosclerosis as revealed by periodic acid Schiff staining and expression of collagen I and fibronectin was significantly reduced by MSC treatment. Oxidative stress was also markedly inhibited in the MSCs group. Furthermore, the expression of TGF-β and membrane localization of GLUT1 were also down-regulated by MSCs. MSCs secreted a significant amount of hepatocyte growth factor (HGF). In vitro, MSC conditioned medium inhibited up-regulation of TGF-β expression stimulated by high glucose and HGF neutralizing antibody blocked the inhibitory effect of MSC conditioned medium.
  
  
  CONCLUSIONS
  MSC treatment reduced urinary albumin excretion and ameliorated glomerulosclerosis. The mechanisms underlying these effects involved reduced blood glucose levels and cellular glucose uptake mediated by GLUT1, thus inhibiting oxidative stress.
authors: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong, China.
authors: Shasha
authors: S
authors: Lv
authors: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong, China.
authors: Jing
authors: J
authors: Cheng
authors: Department of Endocrinology, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong, China.
authors: Aili
authors: A
authors: Sun
authors: Department of Laboratory, The People's Hospital of Ling County, Dezhou, Shandong, China.
authors: Junhua
authors: J
authors: Li
authors: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong, China.
authors: Weiwei
authors: W
authors: Wang
authors: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong, China. Electronic address: guangj@sdu.edu.cn.
authors: Guangju
authors: G
authors: Guan
authors: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong, China. Electronic address: gangliu@sdu.edu.cn.
authors: Gang
authors: G
authors: Liu
authors: Department of Pneumology, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors: Moran
authors: M
authors: Su
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D003928:Diabetic Nephropathies / Q000097:blood / Q000473:pathology / Q000628:therapy*; D005260:Female; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D001786:Blood Glucose
keywords: Bone marrow mesenchymal stem cells; Diabetic nephropathy; Glucose transporter Type 1; Hepatocyte growth factor; Oxidative stress