Transcriptomic analysis of diabetic kidney disease and neuropathy in mouse models of type 1 and type 2 diabetes

Sarah E. Elzinga, Stephanie A. Eid, Brett A. McGregor, Dae Gyu Jang, Lucy M. Hinder, Jacqueline R. Dauch, John M. Hayes, Hongyu Zhang, Kai Guo, Subramaniam Pennathur, Matthias Kretzler, Frank C. Brosius, Emily J. Koubek, Eva L. Feldman, Junguk Hur

Research output: Contribution to journalArticlepeer-review

Abstract

Diabetic kidney disease (DKD) and diabetic peripheral neuropathy (DPN) are common complications of type 1 (T1D) and type 2 (T2D) diabetes. However, the mechanisms underlying pathogenesis of these complications are unclear. In this study, we optimized a streptozotocin-induced db/+ murine model of T1D and compared it to our established db/db T2D mouse model of the same C57BLKS/J background. Glomeruli and sciatic nerve transcriptomic data from T1D and T2D mice were analyzed by self-organizing map and differential gene expression analysis. Consistent with prior literature, pathways related to immune function and inflammation were dysregulated in both complications in T1D and T2D mice. Gene-level analysis identified a high degree of concordance in shared differentially expressed genes (DEGs) in both complications and across diabetes type when using mice from the same cohort and genetic background. As we have previously shown a low concordance of shared DEGs in DPN when using mice from different cohorts and genetic backgrounds, this suggests that genetic background may influence diabetic complications. Collectively, these findings support the role of inflammation and indicate that genetic background is important in complications of both T1D and T2D.

Original languageEnglish (US)
Article numberdmm050080
JournalDMM Disease Models and Mechanisms
Volume16
Issue number10
DOIs
StatePublished - Oct 2023
Externally publishedYes

Keywords

  • Diabetes
  • Diabetic kidney disease
  • Diabetic peripheral neuropathy
  • Genetic mouse models
  • RNA-seq
  • Self-organizing map

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Medicine (miscellaneous)
  • Immunology and Microbiology (miscellaneous)
  • General Biochemistry, Genetics and Molecular Biology

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