Kidney Week

Abstract: TH-PO275

STAT5 Knockouts Are More Susceptible Than Wildtype Mice to Streptozotocin-Induced AKI

Session Information

• AKI Basic: Inflammation and Transcription
  November 02, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Acute Kidney Injury

• 001 AKI: Basic

Authors

• Coschigano, Karen T., Interdisciplinary Program in Molecular and Cellular Biology, Diabetes Institute and Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, United States

Karen T. Coschigano,

• Bogart, Avery May, The Diabetes Institute, Heritage College of Osteopathic Medicine and the Honors Tutorial College, Ohio University, Athens, Ohio, United States

Avery May Bogart,

• Mcdermott, Amber J., Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, United States

Amber J. Mcdermott,

• Hodgin, Jeffrey B., Department of Pathology, University of Michigan, Ann Arbor, Michigan, United States

Jeffrey B. Hodgin,

• Malgor, Ramiro, Interdisciplinary Program in Molecular and Cellular Biology, Diabetes Institute and Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, United States

Ramiro Malgor,

Background

We have previously shown that mice deleted for the first coding exon of the Signal Transducer and Activator of Transcription 5 genes (STAT5 A/B knockout or SKO) exhibit more kidney damage in comparison to wildtype (WT) littermates when examined 12 weeks after treatment with streptozotocin (STZ) to induce diabetes. However, it was not clear whether the kidney damage was a result of the STZ treatment or the resulting hyperglycemia. To try to address this question, this study sought to investigate the acute effects of STZ treatment on kidneys of SKO and WT mice.

Methods

SKO and WT mice received, on five consecutive days, an intraperitoneal injection of either vehicle (citrate buffer, V), STZ (50 mg/kg, M) or four daily injections of vehicle followed on the fifth day by a single dose of STZ (250 mg/kg, H). All mice (n=7/group) were euthanized three days after the last injection and serum and kidneys collected. A portion of each kidney was fixed in formalin and then embedded in paraffin for morphometric and in situ hybridization analyses. The remaining portions of kidneys were flash frozen in liquid nitrogen for gene expression analyses (real-time reverse transcription – polymerase chain reaction; RT-RT/PCR). Two-way (genotype vs. treatment) analysis of variance followed by Tukey post-hoc analysis was used to determine statistical significance at p<0.05.

Results

At the end of the study, blood glucose levels were significantly elevated in the four STZ treatment groups in comparison to the two vehicle groups (WT-V and SKO-V), with the high dose STZ SKO group (SKO-H) being significantly higher than the other three STZ treatment groups (WT-M, SKO-M, WT-H). Blood urea nitrogen and creatinine levels were significantly elevated in the SKO-H group in comparison to the other two SKO treatment groups and to the WT-H group. Histochemical analyses revealed the greatest degree of damage, mainly tubular necrosis with no glomerular damage, in the SKO-H group, with corresponding increased RNA expression of the genes for neutrophil gelatinase-associated lipocalin (NGAL) and cytokines interleukin-6 (IL6) and -1beta (IL1beta).

Conclusion

SKO mice are more susceptible than WT mice to the acute effects of STZ, especially when administered in a single high dose.