J Korean Diabetes Assoc JKDA The Journal of Korean Diabetes Association 1015-6461 Korean Diabetes Association 10.4093/jkda.2007.31.6.451 Review The Role of Glomerular Podocytes in Diabetic Nephropathy Lee Eun-Young Chung Choon Hee 1 2 Department of Internal Medicine, Soonchunhyang University, Korea. Department of Internal Medicine, Yonsei University Wonju College of Medicine, Korea. Institute of Lifelong Health, Yonsei University Wonju College of Medicine, Korea. 11 2007 30 11 2007 31 6 451 454 Copyright © 2007 Korean Diabetes Association 2007

Diabetic nephropathy is the most common cause of end-stage renal disease and accounts for significant morbidity and mortality among individuals with diabetes mellitus. Therefore, the clarification of the pathogenesis of diabetic nephropathy is an urgent issue. Podocytes cover the outer layer of the glomerulus and maintain its integrity so that fluid and toxins exit in urine, but cells and important proteins are kept in the blood stream. Diabetes mellitus alters this structure, it becomes scarred and then the ability of the kidney to clear toxins is lost. Recent evidence shows that early in diabetes the podocyte number is reduced, areas of the glomerular basement membrane are denuded, and podocyte number predicts long-term urinary albumin excretion in the patients with diabetes and microalbuminuria. These results suggest that podocytes play a critical role in the early stage of diabetic nephropathy. It is the purpose of this article to review the pathogenetic role of podocytes in diabetic nephropathy.

 Diabetic nephropathy Podocytes Microalbuminuria Atlas of End-Stage Renal Disease in the United States US Renal Data System USRDS 2007 Annual Data Report 2007 Bethesda, MD National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases Michaud JL Kennedy CR The podocyte in health and disease: insights from the mouse Clin Sci 2007 112 325 323 Lee EY Lee MY Hong SW Chung CH Hong SY Blockade of oxidative stress by vitamin C ameliorates albuminuria and renal sclerosis in experimental diabetic rats Yonsei Med J 2007 48 847 855 Wang A Ziyadeh FN Lee EY Pyagay PE Sung SH Sheardown SA Laping NJ Chen S Interference with TGF-β signaling by Smad3-knockout in mice limits diabetic glomerulosclerosis without affecting albuminuria Am J Physiol Renal Physiol 2007 293 F1657 F1665 Bjorn SF Bangstad HJ Hanssen KF Nyberg G Walker JD Viberti GC Osterby R Glomerular epithelial foot processes and filtration slits in IDDM patients Diabetologia 1995 38 1197 1204 Ellis EN Steffes MW Chavers B Mauer SM Observations of glomerular epithelial cell structure in patients with type I diabetes mellitus Kidney Int 1987 32 736 741 Pagtalunan ME Miller PL Jumping-Eagle S Nelson RG Myers BD Rennke HG Coplon NS Sun L Meyer TW Podocyte loss and progressive glomerular injury in type II diabetes J Clin Invest 1997 99 342 348 Meyer TW Bennett PH Nelson RG Podocyte number predicts long-term urinary albumin excretion in Pima Indians with Type II diabetes and microalbuminuria Diabetologia 1999 42 1341 1344 Lee EY Chung CH Kim JH Joung HJ Hong SY Antioxidants ameliorate the expression of vascular endothelial growth factor mediated by protein kinase C in diabetic podocytes Nephrol Dial Transplant 2006 21 1496 1503 Lee EY Shim MS Kim MJ Hong SY Shin YG Chung CH Angiotensin II receptor blocker attenuates overexpression of vascular endothelial growth factor in diabetic podocytes Exp Mol Med 2004 36 65 70 Mitu GM Wang S Hirschberg R BMP7 is a podocyte survival factor and rescues podocytes from diabetic injury Am J Physiol Renal Physiol 2007 293 F1641 F1648 Kim MJ Lee EY Lee MY Chung CH Adipobiology of diabetes mellitus Immunology, Endocrine and Metabolic Agents in Medicinal Chemistry 2007 7 123 127 Lee EY Chung CH Wang A Pyagay P Chen S Podocyte-derived MCP-1 is stimulated by TGF-β and might contribute to diabetic nephropathy J Am Soc Nephrol 2007 18 655A 656A (abstract) Nakamura T Ushiyama C Shimada N Sekizuka K Ebihara I Hara M Koide H Effect of the antiplatelet drug dilazep dihydrochloride on urinary podocytes in patients in the early stage of diabetic nephropathy Diabetes Care 2000 23 1168 1171 Gu L Ni Z Qian J Tomino Y Pravastatin inhibits carboxymethyllysine-induced monocyte chemoattractant protein 1 expression in podocytes via prevention of signaling events Nephron Exp Nephrol 2007 106 e1 e10

The glomerular urinary filtration barrier in normal non-diabetic rat. Representative photograph of electron microscopy shows three layers of urinary filtration barrier, the fenestrated glomerular endothelium (E), the glomerular basement membrane (BM), and the slit diaphragm of the podocyte. Magnification, × 40,000 [Permission from Lee et al. (reference 4)].

Podocyte injury in diabetic rats. Representative electron photomicrographs show examples of effaced podocytes (P) and decreased number of slit pores (arrows) in the diabetic rats. Magnification, × 40,000 [Permission from Lee et al. (reference 4)].