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Abstract: SA-PO404

Comparative Transcriptome Analysis of Spontaneously Diabetic Torii Fatty Rat Undergoing Salt Loading Alone or with Unilateral Nephrectomy

Session Information

Category: Diabetic Kidney Disease

  • 701 Diabetic Kidney Disease: Basic

Authors

  • Shirozu, Takahiro, Fujita Health University, Toyoake, Japan
  • Yoshimura, Aya, Fujita Health University, Toyoake, Japan
  • Sakata, Miwa, Fujita Health University, Toyoake, Japan
  • Kugita, Masanori, Fujita Health University, Toyoake, Japan
  • Kumamoto, Kanako, Fujita Health University, Toyoake, Japan
  • Hata, Yuko, Fujita Health University, Toyoake, Japan
  • Sugihara, Eiji, Fujita Health University, Toyoake, Japan
  • Yamaguchi, Tamio, Suzuka University of Medical Science, Suzuka, Japan
  • Takahashi, Kazuo, Fujita Health University, Toyoake, Japan
  • Nagao, Shizuko, Fujita Health University, Toyoake, Japan
Background

The Spontaneously Diabetic Torii (SDT) fatty rat is an animal model for type 2 diabetes and obesity. Salt loading and unilateral nephrectomy developed hypertension and diabetic nephropathy in this model early in the disease process. The current study aimed to identify risk factors for diabetic nephropathy and conduct transcriptome analysis using RNA-seq in SDT fatty and Sprague-Dawley (SD) rats.

Methods

Male SDT fatty and SD rats underwent distilled (Cont) or 0.3% NaCl (Salt) water loading from 10 to 20 weeks of age. Body weight, diet and fluid intake, systolic and diastolic blood pressure, blood glucose, and urine albumin level were assessed. Kidney sections were subjected to pathological analyses by H&E, PAS, and sirius red staining to investigate glomerular lesions and fibrosis. Whole kidney extracts underwent RNA-seq to analyze differentially expressed genes (DEGs) between strains, salt loading, and unilateral nephrectomy (Nx) at 9 weeks of age. Gene ontology (GO) analysis was performed on the DEGs using the DAVID analysis tool.

Results

Although no differences in body weight, diet and fluid intake were observed, blood glucose levels were significantly higher in SDT fatty than in SD rats, regardless of loading. Systolic and diastolic blood pressure, urine albumin, and glomerular lesion and fibrosis scores were significantly higher in SDT fatty (Salt) compared to SDT fatty (Cont), SD (Salt), or SD (Cont) rats. Using RNA-seq analyses, comparison of SDT fatty and SD strains showed 864 DEGs in Cont, 1500 in Salt, and 1599 in Salt/Nx. With respect to salt loading effects, in SDT fatty rats there were 481 DEGs in Cont vs. Salt, 365 in Cont vs. Salt/Nx, and 60 in Salt vs. Salt/Nx, whereas in SD rats, there were 57 DEGs in Cont vs. Salt, 167 in Cont vs. Salt/Nx, and 199 in Salt vs. Salt/Nx. GO analysis showed higher expression of genes involved in immune response and extracellular matrix related with inflammation in SDT fatty Salt or Salt/Nx compared to Cont rats.

Conclusion

Salt-treated SDT fatty rats showed elevated expression of inflammatory-related genes. This suggests a potential role of salt in promoting renal pathology in this model.

Funding

  • Government Support – Non-U.S.