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Transforming Growth Factor-β Signal Transduction in the Pathogenesis of Diabetic Nephropathy

Identifying Molecular Targets for Therapeutic Intervention
  • Sheldon Chen
  • Fuad N. Ziyadeh
Part of the Contemporary Diabetes book series (CDI)

Abstract

The pathogenesis of diabetic nephropathy (DN) can be broadly divided into hemodynamic and metabolic causes, but this chapter will focus on the metabolic theories. Among the numerous metabolic derangements in diabetes, the abnormality that plays a central role in the pathogenesis of diabetic renal disease is overactivity of the renal transforming growth factor (TGF)-β system. TGF-β can be thought of as a growth factor or cytokine that causes cellular hypertrophy and stimulates the production of extracellular matrix (ECM), i.e., proteins such as fibronectin, proteoglycans, and several collagen isotypes. These actions are especially relevant to DN, a disease characterized by glomerular and tubular hypertrophy and ECM accumulation. The consequences of matrix buildup manifest as arteriolar hyalinosis, glomerular basement membrane thickening, mesangial matrix expansion (glomerulosclerosis), and tubulo-interstitial fibrosis. In turn, these sclerotic lesions are thought to contribute to progressive renal dysfunction by obliterating the glomerular capillary loops and by displacing or destroying the tubulo-interstitium, causing loss of nephron mass and progressive kidney dysfunction.

Keywords

Diabetic Nephropathy Diabetic Kidney Disease Human Mesangial Cell Mesangial Matrix Expansion Smad7 Promoter 
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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Copyright information

© Humana Press Inc., Totowa, NJ 2006

Authors and Affiliations

  • Sheldon Chen
    • 1
  • Fuad N. Ziyadeh
    • 1
    • 2
  1. 1.Renal-Electrolyte and Hypertension Division, Department of Medicine and the Penn Center for the Molecular Studies of Kidney DiseasesUniversity of PennsylvaniaPhiladelphia
  2. 2.Faculty of MedicineAmerican University of BeirutBeirutLebanon

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