American Journal of Kidney Diseases
Volume 54, Issue 4 , Pages 590-593 , October 2009

Epithelial-Mesenchymal Transition and Podocyte Loss in Diabetic Kidney Disease

  • Kimberly Reidy, MD
  • ,
  • Katalin Susztak, MD, PhD

      Affiliations

    • Corresponding Author InformationAddress correspondence to Katalin Susztak, MD, PhD, Ullman Bldg 619, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461

References 

  1. Huber TB, Hartleben B, Winkelmann K, et al. Loss of podocyte aPKClambda/iota causes polarity defects and nephrotic syndrome. J Am Soc Nephrol. 2009;20:798–806
  2. Reiser J, Kriz W, Kretzler M, Mundel P. The glomerular slit diaphragm is a modified adherens junction. J Am Soc Nephrol. 2000;11:1–8
  3. Pavenstadt H, Kriz W, Kretzler M. Cell biology of the glomerular podocyte. Physiol Rev. 2003;83:253–307
  4. Pagtalunan ME, Miller PL, Jumping-Eagle S, et al. Podocyte loss and progressive glomerular injury in type II diabetes. J Clin Invest. 1997;99:342–348
  5. Kim YH, Goyal M, Kurnit D, et al. Podocyte depletion and glomerulosclerosis have a direct relationship in the PAN-treated rat. Kidney Intl. 2001;60:957–968
  6. Petermann AT, Pippin J, Krofft R, et al. Viable podocytes detach in experimental diabetic nephropathy: Potential mechanism underlying glomerulosclerosis. Nephron. 2004;98:e114–e123
  7. Li JH, Huang XR, Zhu HJ, et al. Advanced glycation end products activate Smad signaling via TGF-beta-dependent and independent mechanisms: Implications for diabetic renal and vascular disease. FASEB J. 2004;18:176–178
  8. Szabo C, Biser A, Benko R, Bottinger E, Susztak K. Poly(ADP-ribose) polymerase inhibitors ameliorate nephropathy of type 2 diabetic Leprdb/db mice. Diabetes. 2006;55:3004–3012
  9. Niranjan T, Bielesz B, Gruenwald A, et al. The Notch pathway in podocytes plays a role in the development of glomerular disease. Nat Med. 2008;14:290–298
  10. Wolf G, Chen S, Ziyadeh FN. From the periphery of the glomerular capillary wall toward the center of disease: Podocyte injury comes of age in diabetic nephropathy. Diabetes. 2005;54:1626–1634
  11. Schiffer M, Bitzer M, Roberts IS, et al. Apoptosis in podocytes induced by TGF-beta and Smad7. J Clin Invest. 2001;108:807–816
  12. Doublier S, Salvidio G, Lupia E, et al. Nephrin expression is reduced in human diabetic nephropathy: Evidence for a distinct role for glycated albumin and angiotensin II. Diabetes. 2003;52:1023–1030
  13. Susztak K, Ciccone E, McCue P, Sharma K, Bottinger EP. Multiple metabolic hits converge on CD36 as novel mediator of tubular epithelial apoptosis in diabetic nephropathy. PLoS Med. 2005;2:e45
  14. Vogelmann SU, Nelson WJ, Myers BD, Lemley KV. Urinary excretion of viable podocytes in health and renal disease. Am J Physiol. 2003;285:F40–F48
  15. Pozzi A, Jarad G, Moeckel GW, et al. Beta1 integrin expression by podocytes is required to maintain glomerular structural integrity. Dev Biol. 2008;316:288–301
  16. Durvasula RV, Shankland SJ. Podocyte injury and targeting therapy: An update. Curr Opin Nephrol Hypertens. 2006;15:1–7
  17. Skoberne A, Konieczny A, Schiffer M. Glomerular epithelial cells in the urine: What has to be done to make them worthwhile?. Am J Physiol. 2009;296:F230–F241
  18. Shankland SJ. The podocyte's response to injury: Role in proteinuria and glomerulosclerosis. Kidney Int. 2006;69:2131–2147
  19. Yamaguchi Y, Iwano M, Suzuki D, et al. Epithelial-mesenchymal transition as a potential explanation for podocyte depletion in diabetic nephropathy. Am J Kidney Dis. 2009;54:653–664
  20. Ziyadeh FN. Mediators of diabetic renal disease: The case for TGF-beta as the major mediator. J Am Soc Nephrol. 2004;15(suppl 1):S55–S57
  21. Bitzer M, Sterzel RB, Bottinger EP. Transforming growth factor-beta in renal disease. Kidney Blood Press Res. 1998;21:1–12
  22. Li Y, Kang YS, Dai C, Kiss LP, Wen X, Liu Y. Epithelial-to-mesenchymal transition is a potential pathway leading to podocyte dysfunction and proteinuria. Am J Pathol. 2008;172:299–308
  23. Li Y, Yang J, Dai C, Wu C, Liu Y. Role for integrin-linked kinase in mediating tubular epithelial to mesenchymal transition and renal interstitial fibrogenesis. J Clin Invest. 2003;112:503–516
  24. Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol. 2006;7:131–142
  25. Yang J, Weinberg RA. Epithelial-mesenchymal transition: At the crossroads of development and tumor metastasis. Dev Cell. 2008;14:818–829
  26. Shankland SJ, Pippin JW, Reiser J, Mundel P. Podocytes in culture: Past, present, and future. Kidney Int. 2007;72:26–36
  27. El-Aouni C, Herbach N, Blattner SM, et al. Podocyte-specific deletion of integrin-linked kinase results in severe glomerular basement membrane alterations and progressive glomerulosclerosis. J Am Soc Nephrol. 2006;17:1334–1344
  28. Dai C, Stolz DB, Bastacky SI, et al. Essential role of integrin-linked kinase in podocyte biology: Bridging the integrin and slit diaphragm signaling. J Am Soc Nephrol. 2006;17:2164–2175
  29. Hirose T, Satoh D, Kurihara H, et al. An essential role of the universal polarity protein, aPKClambda, on the maintenance of podocyte slit diaphragms. PLoS ONE. 2009;4:e4194

PII: S0272-6386(09)00966-4

doi: 10.1053/j.ajkd.2009.07.003

American Journal of Kidney Diseases
Volume 54, Issue 4 , Pages 590-593 , October 2009