Renal hypertrophy is associated with upregulation of TGF-beta 1 gene expression in diabetic BB rat and NOD mouse

Authors:
  • JZJinghong Zhao
    Jinghong Zhao
  • SMSatoshi Miyamoto
    Satoshi Miyamoto
  • YYYoung-Hyun You
    Young-Hyun You
  • JPJung Tak Park
    Jung Tak Park
  • MKMitsuo Kato
    Mitsuo Kato
  • LLLinda Lanting
    Linda Lanting
  • NCNancy Castro
    Nancy Castro
  • BNBo Young Nam
    Bo Young Nam
  • MWMei Wang
    Mei Wang
  • SKShin-Wook Kang
    Shin-Wook Kang
  • RNRama Natarajan
    Rama Natarajan
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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-beta 1 (TGF-beta 1) 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-beta 1 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-beta 1 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-beta 1 transcripts in the livers of the diabetic animals, suggesting that this response is tissue specific. Immunohistochemical studies revealed that TGF-beta 1 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-beta is an early manifestation of the involvement of the kidney by diabetes. Whether increased TGF-beta production in the diabetic kidney is a key promoter of diabetic renal manifestations (e.g., hypertrophy) deserves additional studies.