Potential role of TGF-β in diabetic nephropathy

Brenda B. Hoffman, Knmar Sharma, Fuad N. Ziyadeh

Research output: Contribution to journalReview article

67 Scopus citations

Abstract

Renal injury in diabetes mellitus is a major cause of morbidity and mortality. Several manifestations of diabetic nephropathy may be a consequence of altered production and/or response to cytokines or growth factors. Transforming growth factor-β (TGF-β) is one such factor because it promotes renal cell hypertrophy and regulates the production of extracellular matrix molecules. In addition, high ambient glucose increases TGF-β1 mRNA and protein level in cultured proximal tubular cells and glomerular epithelial and mesangial cells. Neutralizing anti-TGF-β antibodies or antisense TGF-β1 oligodeoxynucleotides prevents the hypertrophic effects of high glucose and the stimulation of matrix synthesis in renal cells. Several reports have described overexpression of TGF-β in the glomeruli and tubulointerstitium of experimental and human diabetes mellitus. We recently provided evidence that the kidney in diabetic patients displays net renal production of immunoreactive TGF-β1, whereas there is net renal extraction in nondiabetic subjects. We also demonstrated that short-term treatment of streptozotocin-diabetic mice with neutralizing monoclonal antibody directed against TGF-β significantly reduces kidney weight and glomerular hypertrophy, and attenuates the increase in extracellular matrix mRNA levels. The factors that mediate increased renal TGF-β activity involve hyperglycemia per se and the intermediary action of other potent mediators such as angiotensin II, thromboxane, endothelins, and platelet-derived growth factor.

Original languageEnglish (US)
Pages (from-to)190-196
Number of pages7
JournalMineral and Electrolyte Metabolism
Volume24
Issue number2-3
DOIs
StatePublished - Mar 1 1998

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Keywords

  • Angiotensin II
  • Collagen
  • Endothelin
  • Glomerulus
  • Glucose
  • Glycation
  • Platelet-derived growth factor
  • Thromboxane
  • Tubulointerstitium

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry

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