title: Autophagy is involved in regulating VEGF during high-glucose-induced podocyte injury.
abstract: Podocytes are the major sites of vascular endothelial growth factor (VEGF) production in kidneys. Over-expression of VEGF is involved in the pathogenesis of diabetic nephropathy (DN), and an emerging body of evidence suggests that autophagy plays an important role in DN. In this study, the effect of autophagy on over-expressed VEGF along with its underlying mechanism was investigated in streptozotocin (STZ)-induced diabetic mice and high glucose (HG)-induced podocytes. We found that diabetes caused podocyte foot process effacement and VEGF upregulation significantly. In vitro, high glucose induced VEGF and reduced the podocyte viability. After treatment with rapamycin in podocytes, an autophagy inducer, VEGF activation was significantly abrogated and podocyte injury was ameliorated. In contrast, podocytes treated with 3-methyladenine (3-MA), a potent autophagy inhibitor, had increased VEGF expression. Furthermore, 3-MA significantly increased the production of HG-induced reactive oxygen species (ROS), whereas rapamycin decreased the cellular ROS level. Inhibition of ROS production by N-acetyl-l-cysteine (NAC) effectively reduced the over-expression of VEGF. These studies show the vital role of autophagy in the regulation of VEGF, which presents a protective effect on HG-induced podocyte injury. ROS production may be an important mechanism for mediating this process.
authors.affiliation: College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University, Tianjin 300071, China. zhuoyang@nankai.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Miaomiao
authors.affiliation: College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University, Tianjin 300071, China. zhuoyang@nankai.edu.cn.
authors.forename: Liu
authors.initials: L
authors.lastname: Chunhua
authors.affiliation: College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University, Tianjin 300071, China. zhuoyang@nankai.edu.cn.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Xiaochen
authors.affiliation: College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University, Tianjin 300071, China. zhuoyang@nankai.edu.cn.
authors.forename: Chen
authors.initials: C
authors.lastname: Xiaoniao
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China. hllin@dlmedu.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Hongli
authors.affiliation: College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University, Tianjin 300071, China. zhuoyang@nankai.edu.cn.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhuo
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects; D001786:Blood Glucose; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000473:pathology; D050533:Glomerular Basement Membrane / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D005947:Glucose / Q000378:metabolism* / Q000633:toxicity; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D005947:Glucose