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Abstract: FR-PO199

Therapeutic Effects of Klotho on Palmitate-Induced Podocyte Damage

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Author

  • Kang, Jeong suk, Soonchunhyang University Cheonan Hospital, Cheonan-si, Chungcheongnam-do, Korea (the Republic of)
Background

Anti-aging gene klotho has been identified as a multi-functional humoral factor and implicated multiple biological processes. However, the effects of klotho on podocyte injury of diabetic nephropathy (DN) are not known. We therefore investigated the renoprotective effects of exogenous klotho on podocyte injury in DN.

Methods

Lipid accumulation and klotho expression were examined in the kidneys from diabetic patient and animals. Cultured podocytes were stimulated with palmitate to induce diabetic mimic condition with or without recombinant klotho (rKL). Western blot, quantitative real time-PCR, immunofluorescence, and albumin permeability analysis were carried out to evaluate the effects of rKL on palmitate-induced podocyte injury.

Results

Glomeruli from diabetic patients showed an increased lipid accumulation. The klotho expression in kidney from diabetic animals and in palmitate-treated podocytes was decreased. Palmitate-treated podocytes increased apoptosis, intracellular ROS, ER stress, inflammation, and fibrosis, and these were significantly attenuated by rKL stimulation. Palmitate-induced downregulation of an antioxidant molecules was ameliorated by rKL. Furthermore, Palmitate-mediated actin cytoskeleton reorganization and increased albumin permeability were recovered significantly by rKL.

Conclusion

The results suggest that palmitate-mediated functional and morphological podocyte injury were recovered by exogenous klotho, and this may implicate klotho as a potential therapeutic target for treatment of podocyte injury of DN.

Funding

  • Government Support - Non-U.S.