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Abstract: PO0679

Alteration of Autophagy-Related Protein 5 (ATG5) Levels and Atg5 Gene Expression in Diabetes Mellitus with and Without Complications

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Nakhoul, Farid M., Galilee Medical Center, Nahariya, Israel
  • Nakhoul, Nakhoul, Faculty of Medicine Bar Ilan University, Ramat-Gan, Israel
  • Farber, Evgeny, The Baruch Padeh Medical Center Poriya, Tiberias, Israel
  • Nakhoul-Armaly, Aida, Diabetes and metabolism Lab Baruch Padeh Poriya Medical Center, Tiberias, Israel
  • Tadmor, Hagar, Faculty of Medicine Bar Ilan University, Ramat-Gan, Israel
Background

Autophagy is a catabolic mechanism that involves lysosomal-dependent degradation of unnecessary or ineffective intracellular components. Autophagy is the process responsible for normal cellular homeostasis, by recycling organelles and proteins. Autophagy pathway and its key participant ATG5 are associated with several pathologies such as diabetes mellitus and its complications.

Methods

Levels and expression of autophagy key components ATG5 and LC3B were analyzed in both human model and murine tissues. One hundred and twenty human subjects were divided into four groups: Healthy (control), diabetic without complications, diabetic nephropathy and diabetic retinopathy. Additionally, we used kidneys from diabetic mice model (WT healthy mice and DN mice, Lysate derived from human peripheral blood mononuclear cells, and murine renal cortex lysates were subjected to western blot analyses of ATG5 and LC3B and immunohistochemical analysis was performed on mice renal tissues.

Results

Western blot and immunohistochemical analysis demonstrate that ATG5 protein levels were significantly decreased in DM, DN and DR patients (0.59±0.07; 0.67±0.06; 0.72±0.06 A.U. units respectively), vs. healthy controls (0.96±0.16 A.U. units), and in DN mice compared to healthy mice (0.65±0.04; 1.15±0.13 A.U. units respectively). Quantification of staining area (%) of ATG5 mice tissue expression also decreased in DN vs. healthy mice (4.42±1.08%; 10.87±1.01% respectively). LC3B levels and expression correlates with ATG5 results: significant reduction in peripheral blood mononuclear cells diabetic patients (with or without complications) vs. healthy controls (0.44±0.05; 0.42±0.035; 0.48±0.06 compared with 0.81±0.05 A.U. units). Renal LC3B levels were lower in DN vs. healthy mice (0.36±0.03; 0.68±0.07 A.U. units). Renal LC3B staining quantification revealed significant reduction in DN vs. healthy mice (1.7±0.23%; 8.56±1.7%).

Conclusion

We conclude that ATG5, as well as LC3B, are down regulated in diabetic patients with or without complications. This diminution contributes to deficiencies in the autophagy process. Our observations show a novel association between autophagy-related protein 5 (ATG5) and diabetic kidney and retinal diseases, with ATG5 as a candidate protein for diabetic nephropathy and retinopathy.