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Abstract: PO0677

Altered Cellular Signaling Pathways Identified by Proteomics and Phosphor-Proteomics in a Rat Model of Diabetic Kidney Disease

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Yoshimura, Aya, Fujita Health University, Toyoake, Aichi, Japan
  • Kugita, Masanori, Fujita Health University, Toyoake, Aichi, Japan
  • Yamaguchi, Hisateru, Yokkaichi Nursing and Medical Care University, Yokkaichi, Mie, Japan
  • Nakajima, Kazuki, Fujita Health University, Toyoake, Aichi, Japan
  • Kumamoto, Kanako, Fujita Health University, Toyoake, Aichi, Japan
  • Yamaguchi, Tamio, Suzuka University of Medical Science, Suzuka, Mie, Japan
  • Takahashi, Kazuo, Fujita Health University, Toyoake, Aichi, Japan
  • Yuzawa, Yukio, Fujita Health University, Toyoake, Aichi, Japan
  • Nagao, Shizuko, Fujita Health University, Toyoake, Aichi, Japan
Background

Alterations of cellular signaling are associated with onset and deterioration of various types of disorders, which could be the targets for new drug development and discovery. Currently, post-translational protein modification and glycosylation are identified by comprehensive proteomic analyses. Since diabetic kidney disease (DKD) is the leading cause of chronic end stage renal disease, exploring novel signaling pathways involved in the initiation and progression of DKD may have therapeutic potential. In the present study, we probed renal tissue in a DKD rat model for altered signaling cascades using proteomics and phosphor-proteomics analyses.

Methods

The animal model of type 2 diabetes mellitus, Spontaneously Diabetic Torii Fatty (SDT Fatty) rats were uninephrectomized at 9 weeks of age, and then from 10 weeks of age, 0.3% NaCl was added to drinking water to exacerbate DKD progression for additional 5 weeks (Group A) or 10 weeks (Group B). After the treatment period, blood was collected for biological measurements and kidney tissue was obtained for histology and proteomics and phosphor-proteomics analyses.

Results

In SDT Fatty rats, the stage of DKD was classified as ‘early’ (Group A) or ‘advanced’ (Group B) by SUN levels and expansion of mesangial matrix and glomerular sclerosis observed by PAS staining. 25 signaling cascades including the PPAR signaling pathway were activated at early stage DKD, and 41 cascades including the proximal tubule bicarbonate reclamation cascade were activated at advanced stage DKD, detected by proteomics analysis in the KEGG database (P<0.05). Further, 33 annotation clusters including the ‘serpin family’ as serine protease inhibitors and the ‘S100 family’ as RAGE ligands were newly detected by functional annotation clustering determination (P<0.05). In addition, five cascades including pathways of ‘microRNA in cancer’ indicated by Crk, Hnrnpk and Marcks at early stage and two cascades including ‘RNA transport’ indicated by Casc3, Eif3b and Eif3c at advanced stage were detected by phosphor-proteomics analysis in KEGG database (P<0.05).

Conclusion

These findings demonstrate that several groups of known and new signaling cascades may have important roles for the initiation and/or progression of DKD.

Funding

  • Government Support – Non-U.S.