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Evidence of apoptosis in human diabetic kidney

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Abstract

Diabetic nephropathy is characterized by an early period of renal growth with glomerular and tubular cell hypertrophy, but this is followed by progressive glomerulosclerosis and tubulointerstitial fibrosis, associated with loss of renal tissue. We studied whether apoptotic cell death occurs in human diabetic nephropathy. Percutaneous renal biopsy samples were obtained from five patients with diabetic nephropathy who were receiving insulin and/or angiotensin-converting enzyme inhibitor therapy. Apoptosis was determined by the presence of DNA fragmentation, detected by in situ TUNEL staining, and by characteristic features on electron microscopy, such as chromatin condensation. Apoptosis was present in all five biopsy specimens, either in epithelial cells of the proximal or distal tubules, or in endothelial cells or interstitial cells. No apoptosis was detected in cells of the glomeruli. The present study provides evidence for apoptosis in human diabetic kidney, and suggests a role for apoptosis in the gradual loss of renal mass.

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References

  1. Wolf G, Ziyadeh FN: The role of angiotensin II in diabetic nephropathy: Emphasis on nonhemodynamic mechanisms. Am J Kidney Dis 29: 153-163, 1997

    PubMed  Google Scholar 

  2. Kumar D, Lou H, Singal PK: Oxidative stress and apoptosis in heart dysfunction. Herz 27: 662-668, 2002

    Article  PubMed  Google Scholar 

  3. Woo D: Apoptosis and loss of renal tissue in polycystic kidney diseases. N Engl J Med 333: 18-25, 1995

    Article  PubMed  Google Scholar 

  4. Daemen MA, van V, Denecker G, Heemskerk VH, Wolfs TG, Clauss M, Vandenabeele P, Buurman WA: Inhibition of apoptosis induced by ischemia reperfusion prevents inflammation. J Clin Invest 104: 541-549, 1999

    PubMed  Google Scholar 

  5. Morrissey JJ, Klahr S: Effect of AT2 receptor blockade on the pathogenesis of renal fibrosis. Am J Physiol 276: F39-F45, 1999

    PubMed  Google Scholar 

  6. Shimizu A, Kitamura H, Masuda Y, Ishizaki M, Sugisaki Y, Yamanaka N: Apoptosis in the repair process of experimental proliferative glomerulonephritis. Kidney Int 47: 114-121, 1995

    PubMed  Google Scholar 

  7. Baker AJ, Mooney A, Hughes J, Lombardi D, Johnson RJ, Savill J: Mesangial cell apoptosis: The major mechanism for resolution of glomerular hypercellularity in experimental mesangial proliferative nephritis. J Clin Invest 94: 2105-2116, 1994

    PubMed  Google Scholar 

  8. Schelling JR, Cleveland RP: Involvement of Fas-dependent apoptosis in renal tubular epithelial cell deletion in chronic renal failure. Kidney Int 56: 1313-1316, 1999

    Article  PubMed  Google Scholar 

  9. Sugiyama H, Kashihara N, Makino H, Yamasaki Y, Ota A: Apoptosis in glomerular sclerosis. Kidney Int 49: 103-111, 1996

    PubMed  Google Scholar 

  10. Ortiz A, Ziyadeh FN, Neilson EG: Expression of apoptosis-regulatory genes in renal proximal tubular epithelial cells exposed to high ambient glucose and in diabetic kidneys. J Investig Med 45: 50-56, 1997

    PubMed  Google Scholar 

  11. Kelly DJ, Cox AJ, Tolcos M, Cooper ME, Wilkinson-Berka JL, Gilbert RE: Attenuation of tubular apoptosis by blockade of the renin-angiotensin system in diabetic Ren-2 rats. Kidney Int 61: 31-39, 2002

    Article  PubMed  Google Scholar 

  12. Lorenzi M, Montisano DF, Toledo S, Barrieux A: High glucose induces DNA damage in cultured human endothelial cells. J Clin Invest 77: 322-325, 1986

    PubMed  Google Scholar 

  13. Moudgil R, Menon V, Xu Y, Musat-Marcu S, Kumar D, Jugdutt BI: Postischemic apoptosis and functional recovery after angiotensin II type 1 receptor blockade in isolated working rat hearts. J Hypertens 19: 1121-1129, 2001

    Article  PubMed  Google Scholar 

  14. Fiordaliso F, Li B, Latini R, Sonnenblick EH, Anversa P, Leri A, Kajstura J: Myocyte death in streptozotocin-induced diabetes in rats in angiotensin II-dependent. Lab Invest 80: 513-527, 2000

    PubMed  Google Scholar 

  15. Barber AJ, Lieth E, Khin SA, Antonetti DA, Buchanan AG, Gardner TW: Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin. J Clin Invest 102: 783-791, 1998

    PubMed  Google Scholar 

  16. Jonassen AK, Brar BK, Mjos OD, Sack MN, Latchman DS, Yellon DM: Insulin administered at reoxygenation exerts a cardioprotective effect in myocytes by a possible anti-apoptotic mechanism. J Mol Cell Cardiol 32: 757-764, 2000

    Article  PubMed  Google Scholar 

  17. Chevalier RL, Thornhill BA, Wolstenholme JT: Renal cellular response to ureteral obstruction: Role of maturation and angiotensin II. Am J Physiol 277: F41-F47, 1999

    PubMed  Google Scholar 

  18. Ortiz A, Lorz C, Catalan MP, Danoff TM, Yamasaki Y, Egido J, Neilson EG: Expression of apoptosis regulatory proteins in tubular epithelium stressed in culture or following acute renal failure. Kidney Int 57: 969-981, 2000

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Cardiovascular Research Centre, Department of Medicine, University of Wisconsin, Madison, WI, USA

    Dinender Kumar

  2. Department of Laboratory Medicine, Ottawa Hospital, Ottawa, Ontario, Canada, K1H 8L6

    Susan Robertson

  3. Department of Cellular and Molecular Medicine and Department of Medicine, Division of Nephrology, Kidney Research Centre, Ottawa Health Research Institute, University of Ottawa, ON, Canada

    Kevin D. Burns

Authors
  1. Dinender Kumar
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  2. Susan Robertson
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  3. Kevin D. Burns
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Kumar, D., Robertson, S. & Burns, K.D. Evidence of apoptosis in human diabetic kidney. Mol Cell Biochem 259, 67–70 (2004). https://doi.org/10.1023/B:MCBI.0000021346.03260.7e

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  • DOI: https://doi.org/10.1023/B:MCBI.0000021346.03260.7e

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