Reduction in podocyte density as a pathologic feature in early diabetic nephropathy in rodents: Prevention by lipoic acid treatment

被引：83

作者：

Siu B. ^{[1
]}

Saha J. ^{[1
]}

Smoyer W.E. ^{[2
]}

Sullivan K.A. ^{[3
]}

Brosius III F.C. ^{[1
]}

机构：

[1] Departments of Internal Medicine and Physiology, University of Michigan, 1560 MSRB2, Ann Arbor, MI 48109-0676

[2] Department of Pediatrics, University of Michigan, 8220E MSRB III, Ann Arbor

[3] Department of Neurology, University of Michigan, Ann Arbor, MI 48109-0580

来源：

BMC Nephrology | / 7卷 / 1期

关键词：

Diabetic Nephropathy; Podocyte Injury; Podocyte Damage; Podocyte Loss; Podocyte Number;

D O I：

10.1186/1471-2369-7-6

中图分类号：

学科分类号：

摘要：

Background: A reduction in the number of podocytes and podocyte density has been documented in the kidneys of patients with diabetes mellitus. Additional studies have shown that podocyte injury and loss occurs in both diabetic animals and humans. However, most studies in animals have examined relatively long-term changes in podocyte number and density and have not examined effects early after initiation of diabetes. We hypothesized that streptozotocin diabetes in rats and mice would result in an early reduction in podocyte density and that this reduction would be prevented by antioxidants. Methods: The number of podocytes per glomerular section and the podocyte density in glomeruli from rats and mice with streptozotocin (STZ)-diabetes mellitus was determined at several time points based on detection of the glomerular podocyte specific antigens, WT-1 and GLEPP1. The effect of insulin administration or treatment with the antioxidant, α-lipoic acid, on podocyte number was assessed. Results: Experimental diabetes resulted in a rapid decline in apparent podocyte number and podocyte density. A significant reduction in podocytes/glomerular cross-section was found in STZ diabetes in rats at 2 weeks (14%), 6 weeks (18%) and 8 weeks (34%) following STZ injection. Similar declines in apparent podocyte number were found in STZ diabetes in C57BL/6 mice at 2 weeks, but not at 3 days after injection. Treatment with α-lipoic acid substantially prevented podocyte loss in diabetic rats but treatment with insulin had only a modest effect. Conclusion: STZ diabetes results in reduction in apparent podocyte number and in podocyte density within 2 weeks after onset of hyperglycemia. Prevention of these effects with antioxidant therapy suggests that this early reduction in podocyte density is due in part to increased levels of reactive oxygen species as well as hyperglycemia. © 2006Siu et al; licensee BioMed Central Ltd.

引用

页数：11

共 22 条

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