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Abstract: FR-PO348

Inhibition of Fatty Acid-Binding Protein 4 Protects Renal Tubular Epithelial Cells and Rescues Diabetic Kidney Disease

Session Information

Category: Diabetic Kidney Disease

  • 701 Diabetic Kidney Disease: Basic

Authors

  • Wu, Yen-Wen, Far Eastern Memorial Hospital, New Taipei City, Taiwan
  • Chen, Jaw-Wen, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan
  • Chang, Ting-Ting, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan
Background

Previous clinical observations have shown that increased circulating fatty acid binding protein (FABP) 4 is associated with the progression of diabetic kidney disease (DKD) in patients with type 2 diabetes. This study aimed to investigate the potential mechanistic role of FABP4 and the direct effects of FABP4 inhibition in experimental DKD.

Methods

To mimic the presence of hyperglycemia in DKD, human renal proximal tubular epithelial cells were cultured with high glucose (25 mM) for 3 days for in vitro study. In addition, Leprdb/JNarl type 2 DM mice were used for a mouse model of DKD. Mice were randomly assigned to receive an oral FABP4 inhibitor, BMS-309403, for 2 weeks.

Results

Administration of FABP4 inhibitor reduced the high glucose-induced apoptosis of renal proximal tubular epithelial cells. Furthermore, FABP4 inhibitor attenuated high glucose-induced inflammatory protein (tumor necrosis factor-α/interleukin-1β/interleukin-6) and fibrotic protein (transforming growth factor-β/collagen-1) expressions in vitro. In in vivo study, treatment of FABP4 inhibitor reduced the increase of serum blood urea nitrogen and creatinine levels in DKD mice. Moreover, the urinary albumin-to-creatinine ratio and kidney-to-body weight ratio were attenuated by FABP4 inhibitor treatments.

Conclusion

Taken together, inhibition of FABP4 could protect renal proximal tubular epithelial cells against the high glucose-induced damage in vitro and improve renal function, renal hypertrophy, and urinary albumin-to-creatinine ratios in DKD mice in vivo. Further molecular mechanistic insights may be explored to provide a novel theoretical basis for the potential therapeutic target of FABP4 in DKD.