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Abstract: TH-PO877

Early Changes in Kidney Transcriptomics and Proteomics in Streptozotocin-Induced Diabetes Model

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Barreiro, Karina A., Institute for Molecular Medicine Finland FIMM, University of Helsinki,, Helsinki, Finland
  • Jouppila, Annukka, Helsinki University Hospital Clinical Research Institute, Helsinki, Finland
  • Leparc, German G., Boehringer-Ingelheim, Biberach, Germany
  • Delic, Denis, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
  • Lassila, Riitta, Helsinki University Hospital, Helsinki, Finland
  • Huber, Tobias B., University Medical Center Hamburg, Hamburg, Germany
  • Holthofer, Harry B., University of Helsinki, Finnish Institute of Molecular Medicine, Helsinki, Finland
Background

Diabetic kidney disease (DKD) is a progressive and feared microvascular damage in diabetes patients. It is the leading cause of end-stage kidney disease (ESKD) globally. There is strong evidence that cellular insulin resistance is a major driver of DKD progression. However, early pathways involved in the development of DKD are still poorly understood. Here we explored transcriptomics and proteomics of kidney tissue in streptozotocin (STZ) induced diabetic rat kidneys in order to confirm known and establish new early molecular changes associated with DKD.

Methods

To induce diabetes, one dose of STZ (50mg/kg) was administered in the intraperitoneal cavity to animals fasted overnight. Urine and kidneys were collected at days 1, 7 and 15 post injection. Sections cut of kidney cortex were used to isolate RNA and proteins. RNA was isolated using RNeasy Fibrous Tissue and subjected to small and long RNA sequencing. For protein analysis, tissue was homogenized in 7M urea, 2M thiourea, 4% CHAPS using Percellys® 24 homogenizer and subjected to LC-HDMS.

Results

1 day after injection of STZ, an increase of in serum glucose levels and urine volumes was detected in STZ treated groups as expected.Distinct differences between diabetic and control groups in regard to miRNA, mRNA and proteins, respectively, were observed as early as day seven and also at day 15 post injection.At day 15, the gene enrichment analysis (GO: Biological process) of proteins reflected many known pathways involved in diabetes type II. These included pathways modulated at the onset of diabetes and those associated e.g. with glycolysis/gluconeogenesis and others. An exclusive transcriptional expression pattern was seen at each timepoint which should be very valuable to establish new molecular targets now available for verification in human DKD.

Conclusion

Our approach describes early molecular changes of DKD at transcriptomics and proteomics level. These results are valuable to define previously unidentified pathways involved and novel molecular targets in DKD.