Potential role of TGF-β in diabetic nephropathy

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

Research output: Contribution to journalReview article

67 Citations (Scopus)

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
Externally publishedYes

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Diabetic Nephropathies
Transforming Growth Factors
Kidney
Medical problems
Hypertrophy
Extracellular Matrix
Glucose
Messenger RNA
Mesangial Cells
Experimental Diabetes Mellitus
Oligodeoxyribonucleotides
Thromboxanes
Platelet-Derived Growth Factor
Endothelins
Streptozocin
Neutralizing Antibodies
Angiotensin II
Hyperglycemia
Intercellular Signaling Peptides and Proteins
Diabetes Mellitus

Keywords

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

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry

Cite this

Potential role of TGF-β in diabetic nephropathy. / Hoffman, Brenda B.; Sharma, Kumar; Ziyadeh, Fuad N.

In: Mineral and Electrolyte Metabolism, Vol. 24, No. 2-3, 01.03.1998, p. 190-196.

Research output: Contribution to journalReview article

Hoffman, Brenda B. ; Sharma, Kumar ; Ziyadeh, Fuad N. / Potential role of TGF-β in diabetic nephropathy. In: Mineral and Electrolyte Metabolism. 1998 ; Vol. 24, No. 2-3. pp. 190-196.
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