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박종보Jong Bo Park
서울대학교, 그래핀스퀘어 케미컬
Adv. Sci., 30 December 2024 | https://doi.org/10.1002/advs.202410747
Effects of Graphene Quantum Dots on Renal Fibrosis Through Alleviating Oxidative Stress and Restoring Mitochondrial Membrane Potential
Kyu Hong Kim 1,†, Jong Bo Park 2,3,†, Jung Nam An 4,†, Gaeun Bae 2, Kyu Hyeon Kim 1, Seong Joon Park 1, Youngjin Jung 2, Yong Chul Kim 5, Jung Pyo Lee 6, Jae Wook Lee 7, Dong Ki Kim 5,8, Yon Su Kim 5,8,*, Byung Hee Hong 2,9,* and Seung Hee Yang 8,*
1Department of Biomedical Sciences Seoul National University Seoul, South Korea
2Department of Chemistry, College of Natural Sciences Seoul National University Seoul, South Korea
3R&D Center of Graphene Square Chemical Inc. Seoul, South Korea
4Department of Internal Medicine Hallym University Sacred Heart Hospital Anyang, South Korea
5Department of Internal Medicine Seoul National University Hospital Seoul, South Korea
3R&D Center of Graphene Square Chemical Inc. Seoul, South Korea
4Department of Internal Medicine Hallym University Sacred Heart Hospital Anyang, South Korea
5Department of Internal Medicine Seoul National University Hospital Seoul, South Korea
6Department of Internal Medicine Seoul National University Boramae Medical Center Seoul, South Korea
7Nephrology Clinic National Cancer Center Goyang, South Korea
7Nephrology Clinic National Cancer Center Goyang, South Korea
8Department of Kidney Research Institute Seoul National University Medical Research Center Seoul, South Korea
9Graduate School of Convergence Science and Technology Seoul National University Suwon, South Korea
10Biomedical Research Institute Seoul National University Hospital Seoul, South Korea
†K.H.K., J.B.P., and J.N.A. contributed equally to this work.
*Corresponding authors: correspondence to Yon Su Kim, Byung Hee Hong or Seung Hee Yang
10Biomedical Research Institute Seoul National University Hospital Seoul, South Korea
†K.H.K., J.B.P., and J.N.A. contributed equally to this work.
*Corresponding authors: correspondence to Yon Su Kim, Byung Hee Hong or Seung Hee Yang
Abstract
Podocyte injury and proteinuria in glomerular disease are critical indicators of acute kidney injury progression to chronic kidney disease. Renal mitochondrial dysfunction, mediated by intracellular calcium levels and oxidative stress, is a major contributor to podocyte complications. Despite various strategies targeting mitochondria to improve kidney function, effective treatments remain lacking. This study investigates the potential of graphene quantum dots (GQDs) in mitigating renal fibrosis and elucidates their underlying mechanisms. In animal models of Adriamycin-induced nephropathy and 5/6 subtotal nephrectomy, GQDs treatment exhibits anti-inflammatory, anti-fibrotic, and anti-apoptotic effects by restoring podocyte actin structure. These therapeutic benefits are associated with the downregulation of transient receptor potential channel 5 (TRPC5) activity, which is related to kidney fibrosis and mitochondrial dysfunction. In vitro, GQDs suppress TRPC5, enhancing anti-fibrotic and anti-apoptotic effects by lowering calcium levels under oxidative stress and mechanical pressure. Anti-oxidative and anti-senescent effects are also confirmed. Most significantly, transcriptomics and electron microscopy analyses reveal that GQD treatment enhances mitochondrial respiration-related gene profiles and improves mitochondrial cristae morphology. These findings suggest that GQDs are a promising therapeutic nanomaterial for renal cell damage, capable of modulating calcium-dependent apoptosis associated with mitochondrial injury, potentially slowing fibrosis progression.
논문정보
- Research article
- 2024년 12월 (BRIC 등록일 2025-02-12)
- 국내 연구진
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