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Abstract: SA-PO227

Sex Differences in Renal Physiological Parameters and Kidney Expression of NOX-4, TGF-β, and Fibronectin in Mice With Streptozotocin (STZ)-Induced Diabetes Mellitus

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Gonzalez, Alexis A., Pontificia Universidad Catolica de Valparaiso, Valparaiso, Valparaiso, Chile
  • Lazcano-Páez, Geraldine Mabel Ignacia, Pontificia Universidad Catolica de Valparaiso, Valparaiso, Valparaiso, Chile
  • Cárdenas, Pilar, Pontificia Universidad Catolica de Valparaiso, Valparaiso, Valparaiso, Chile
  • Casado-Barragán, Felipe Sebastián, Pontificia Universidad Catolica de Valparaiso, Valparaiso, Valparaiso, Chile

Group or Team Name

  • Group of Renal Physiology and Biochemistry
Background

A hallmark of DM is the hyperglycemia but also hyperglycosuria, along with the presence of proteinuria and signs of renal damage that includes deposition of extracellular matrix, glomerular damage and tubulointerstitial fibrosis. All these aspects are usually observed during advanced stages of the disease. Among the markers observed in chronic DM in experimental animal models, the profibrotic factors transforming growth factor-beta 1 (TGF-β1), fibronectin and renal NADPH oxidase (NOX)-4 which contributes to increased reactive oxygen species (ROS) generation, are mostly responsible for the profibrotic phenotype in tubular cells enhancing the proliferation of fibroblasts and collagen deposition. Most of the diabetic animal models described in the literature analyzed the effects of chronic DM on renal physiology or kidney injury markers. Sex differences in glucose metabolism in animal models of DM have been described. Furthermore, it is known that women and man with DM have alterations in sex hormones. Our aim was to evaluate the physiological parameters and kidney expression of TGF-β1, fibronectin and NOX-4 in male and female mice with streptozotocin (STZ)-induced DM during 6 days.

Methods

CF-1 male or female mice were injected with or without STZ (150 mg/kg) in a single dose. Levels of fasting blood glucose (FBG), sodium excretion and urine protein/creatinine were measured at 0, 3 and 6 days. After 6 days of treatment the animals were euthanized and kidneys were removed to evaluate TGF-β1, fibronectin and NOX-4 expression by immunoblotting, qRT-PCR and immunofluorescence.

Results

Despite the augmentation in FBG in STZ male and female mice, males showed significantly higher levels than females at day 3. STZ males also showed higher urinary protein vs. creatinine levels that STZ females. Males sowed a slight but significant sodium retention. STZ males showed higher expression of fibronectin as compared to control mice and also compared to females STZ. By contrast, STZ female mice showed higher expression of TGF-β and NOX-4.

Conclusion

Our data suggest that there are sex differences on the induction of the expression of TGF-β, fibronectin and NOX-4 in mice subjected to (STZ)-induced DM as early as 6 days.