Ceria-Zirconia nanoparticles reduce intracellular globotriaosylceramide accumulation and attenuate kidney injury by enhancing the autophagy flux in cellular and animal models of Fabry disease

Journal of Nanobiotechnology - Tập 20 Số 1
Jong Hun An1, Sang-Eun Hong2, Seong‐Lan Yu3, Jaeku Kang4, Chang Gyo Park4, Hoi Young Lee4, Sung Ki Lee3, Dong Chul Lee5, Hwan‐Woo Park6, Won‐Min Hwang1, Sung-Ro Yun1, Yohan Park1, Moon Hyang Park7, Kuk Ro Yoon2, Se-Hee Yoon1
1Division of Nephrology and Department of Internal Medicine, Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon, Republic of Korea
2Department of Chemistry, Hannam University, Daejeon, Republic of Korea
3Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon, Republic of Korea
4Department of Pharmacology, College of Medicine, Konyang University, Daejeon, Republic of Korea
5Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB),, Deajeon, Republic of Korea
6Department of Cell Biology, Myunggok Medical Research Institute, Konyang University College of Medicine, Daejeon, Republic of Korea
7Department of Pathology, College of Medicine, Konyang University, Daejeon, Republic of Korea

Tóm tắt

AbstractBackgroundFabry disease (FD) is a lysosome storage disease (LSD) characterized by significantly reduced intracellular autophagy function. This contributes to the progression of intracellular pathologic signaling and can lead to organ injury. Phospholipid–polyethyleneglycol-capped Ceria-Zirconia antioxidant nanoparticles (PEG-CZNPs) have been reported to enhance autophagy flux. We analyzed whether they suppress globotriaosylceramide (Gb3) accumulation by enhancing autophagy flux and thereby attenuate kidney injury in both cellular and animal models of FD.ResultsGb3 was significantly increased in cultured human renal proximal tubular epithelial cells (HK-2) and human podocytes following the siRNA silencing of α galactosidase A (α-GLA). PEG-CZNPs effectively reduced the intracellular accumulation of Gb3 in both cell models of FD and improved both intracellular inflammation and apoptosis in the HK-2 cell model of FD. Moreover these particles attenuated pro fibrotic cytokines in the human podocyte model of FD. This effect was revealed through an improvement of the intracellular autophagy flux function and a reduction in reactive oxygen species (ROS). An FD animal model was generated in which 4-week-old maleB6;129-Glatm1Kul/J mice were treated for 8 weeks with 10 mg/kg of PEG-CZNPs (twice weekly via intraperitoneal injection). Gb3 levels were reduced in the kidney tissues of these animals, and their podocyte characteristics and autophagy flux functions were preserved.ConclusionsPEG-CZNPs alleviate FD associated kidney injury by enhancing autophagy function and thus provide a foundation for the development of new drugs to treat of storage disease.Graphical Abstract

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Journal of Nanobiotechnology

Tập 20 Số 1

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