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Abstract: FR-PO401

Metabolomics and In Vitro Validation Study to Identify the Preventive Effect of Sodium-Glucose Cotransporter 2 Inhibitor on the Progression of Diabetic Nephropathy

Session Information

Category: Development‚ Stem Cells‚ and Regenerative Medicine

  • 500 Development‚ Stem Cells‚ and Regenerative Medicine

Authors

  • Jo, Hyung Ah, Inje University Ilsan Paik Hospital, Goyang, Korea (the Republic of)
  • Yang, Seung Hee, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
Background

We aimed to determine the metabolic profile of kidney resident cells under hyperglycemic conditions and following SGLT2 inhibitor treatment. The targeted metabolomics using the Absolute IDQ-p180 kit was applied to quantify metabolites in the kidney resident cells stimulated by high glucose (25, 50 µM) and following SGLT2 inhibitor, dapagliflozin treatment.

Methods

The primary cultured human tubular epithelial cells (TECs), podocytes, and glomerular endothelial cells (GECs) were used to identify metabolomic patterns according to hyperglycemic conditions following dapagliflozin treatment.

Results

The metabolomic pattern of kidney resident cells is distinctly depicted in the hyperglycemic stimuli compared to control (Figure 1).
The levels of Asparagine, PC aa C38:4, and PC ae C34:1 were elevated in the TECs stimulated with 50 µM of glucose and significantly decreased after dapagliflozin treatment. The metabolite level of PC aa C28:1 was decreased in the TECs according to 50 µM of glucose treatment, and dapagliflozin treatment elevated its level. The level C18:1-OH was significantly decreased after 50 µM of glucose compared with control and its level was significantly increased after dapagliflozin treatment in podocytes. The level of C12 in the GECs was decreased after treatment with 50 µM of glucose, whereas dapagliflozin treatment significantly elevated its level. In vitro analysis showed that the treatment with glucose significantly increased the expression of fibronectin dose-dependently assessed by Western blot in the TECs, podocytes, and GECs. Dapagliflozin treatment significantly abrogated the high-glucose-induced increased expression of fibronectin (Figure 2).

Conclusion

The metabolic pattern of renal resident cells after SGLT2 inhibitor treatment is thought to originate from pathways associated with renal anti-fibrosis in diabetic conditions.