Abstract: TH-PO464
Graphene Quantum Dots Suppress Kidney Fibrosis After AKI by Affecting the Pericyte-Myofibroblast Transition
Session Information
- CKD: Mechanisms - I
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Li, Lilin, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
- Yang, Seung Hee, Kidney Research Institute, Seoul National University, Seoul, Korea (the Republic of)
- Joun, Joo Hong, Seoul National University, Seoul, Korea (the Republic of)
- An, Jung Nam, Seoul National University Boramae Medical Center, Seoul, Korea (the Republic of)
- Lee, Jeonghwan, Seoul National University Boramae Medical Center, Seoul, Korea (the Republic of)
- Lee, Jung Pyo, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
Background
Renal pericytes are important in the pathogenesis of kidney disease. They are key to vascular survival can contribute to glomerular and interstitial fibrosis. Graphene quantum dots (GQDs) are novel nanomaterials with excellent biocompatibility. They have anti-oxidative, anti-inflammatory and immune regulatory effects. The purpose of this study is to demonstrate that GQDs can inhibit pericyte activation and reduce the conversion of pericytes into myofibroblasts, thereby suppress kidney fibrosis after acute kidney injury.
Methods
Unilateral ischemia-reperfusion injury (UIRI) was induced in 7- to 8-wk-old male wild-type C57BL6 mice. GQDs were injected in kidney fibrosis models through the tail vein and the animals were observed for 6 wk. Histopathological examination was performed on the kidneys using Masson's trichrome staining, and pericyte detection in tissue by Immunofluorescence technique. rhTGF-β1 was used in vitro experiments to induce pericyte-myofibroblast transition. Western blot analysis was used to detect the expression of fibrotic markers.
Results
At 6 wk after UIRI, GQDs treatment significantly attenuated interstitial fibrosis in UIRI models. GQDs administration significantly reduced the expression of α-smooth muscle actin, collagen I, and fibronectin, vimentin,TGF-beta1, Bax, and increased the expression of E-cadherin, smad7, and bcl2. In addition, the expression of PDGFR in the URI group was significantly increased compared with the control group, only a small part overlapped with NG2, and the overlap was significantly less than that of the normal group and away from the endothelial cells. Compared with the UIRI group, the expression of PDGFR was significantly decreased after GQDs treatment, and the overlap of PDGFR and NG2 was increased, and the signs of pericytes away from endothelial cells were improved. rhTGF-β1 was used in vitro experiments to induce pericyte injury, and the expression of NG2, a-SMA and collagen 1a1 was increased compared with the control group, and the dose-dependent decrease was observed after treatment with various concentrations of GQDs
Conclusion
We found that non-toxic doses of GQDs protect pericyte damage and inhibit the transformation of pericytes into myofibroblasts, there by plays an important role in anti-fibrotic processes after acute kidney injury.