Renal hypertrophy is associated with upregulation of TGF-β1 gene expression in diabetic BB rat and NOD mouse

K. Sharma, F. N. Ziyadeh

Research output: Contribution to journalArticlepeer-review

204 Scopus citations

Abstract

Renal hypertrophy is an early feature of diabetes, and it may predispose the kidney to the eventual development of parenchymal dysfunction. Since we have previously demonstrated that short-term culture in high glucose concentration stimulates production of transforming growth factor-β1 (TGF- β1) in proximal tubular and glomerular mesangial cells, we postulated that this cytokine, which has potent regulatory effects on cellular growth and extracellular matrix production, is important in mediating diabetic renal disease. In this study we evaluated the gene and protein expression of TGF- β1 in the kidney of two rodent models of spontaneous insulin-dependent diabetes mellitus [the biobreeding (BB) rat and the nonobese diabetic (NOD) mouse]. In association with the appearance in both models of significant renal hypertrophy, TGF-β1 mRNA levels were increased threefold in the kidney of the diabetic BB rat after 3 days of diabetes and also threefold after 7-9 days in the NOD mouse. There was no increase in TGF-β1 transcripts in the livers of the diabetic animals, suggesting that this response is tissue specific. Immunohistochemical studies revealed that TGF-β1 protein is concordantly elevated in the cortical tubular cells of the diabetic kidney in both models. These results suggest that the stimulated expression of renal TGF-β is an early manifestation of the involvement of the kidney by diabetes. Whether increased TGF-β production in the diabetic kidney is a key promoter of diabetic renal manifestations (e.g., hypertrophy) deserves additional studies.

Original languageEnglish (US)
Pages (from-to)F1094-F1101
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume267
Issue number6 36-6
StatePublished - 1994
Externally publishedYes

Keywords

  • biobreeding rat
  • diabetic nephropathy
  • kidney hypertrophy
  • nonobese diabetic mouse
  • transforming growth factor- β
  • tubular epithelium

ASJC Scopus subject areas

  • Physiology

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