Transforming Growth Factor-Beta and other Cytokines in Experimental and Human Diabetic Nephropathy

  • Fuad N. Ziyadeh
  • Dong Cheol Han
  • Andras Mogyorosi

Abstract

Increased renal extracellular matrix production in diabetes is most likely the result of increased synthesis and/or decreased degradation rates [1–3]. To model the effects of the diabetic milieu on the kidney, various renal cell lines have been investigated under high ambient glucose concentrations in tissue culture. High glucose stimulates proximal tubular cell hypertrophy [4] and modulates mesangial cell growth [5]. It also stimulates the production of connective tissue molecules such as fibronectin and collagens in proximal tubular cells and in glomerular mesangial, epithelial, and endothelial cells [4, 6–12]. It is noteworthy that periodically elevated glucose levels in rat mesangial cell culture increase collagen production to a greater extent than a sustained elevation in ambient glucose concentration [13]. This may closely mimic the fluctuations of blood glucose levels in vivo. The seminal factor for renal cell damage by high glucose is likely to be intracellular high glucose accumulation and metabolism rather than simply the extracellular, ambient hyperglycemia. Rat mesangial cells transfected with the human glucose transporter GLUTI gene demonstrate stimulated mesangial matrix synthesis despite physiologic extracellular glucose concentration [14].

Keywords

Diabetic Nephropathy Mesangial Cell Proximal Tubular Cell Diabetic Kidney Disease Renal Hypertrophy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Springer Science+Business Media Dordrecht 1998

Authors and Affiliations

  • Fuad N. Ziyadeh
    • 1
  • Dong Cheol Han
    • 1
  • Andras Mogyorosi
    • 1
  1. 1.Penn Center for Molecular Studies of Kidney Diseases, Renal Electrolyte and Hypertension Division, Department of MedicineUniversity of PennsylvaniaPhiladelphiaUSA

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