Effects of Graphene Quantum Dots on Renal Fibrosis Through Alleviating Oxidative Stress and Restoring Mitochondrial Membrane Potential

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. Despi...

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Main Authors: Kyu Hong Kim, Jong Bo Park, Jung Nam An, Gaeun Bae, Kyu Hyeon Kim, Seong Joon Park, Youngjin Jung, Yong Chul Kim, Jung Pyo Lee, Jae Wook Lee, Dong Ki Kim, Yon Su Kim, Byung Hee Hong, Seung Hee Yang
Format: Article
Language:English
Published: Wiley 2025-03-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202410747
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author Kyu Hong Kim
Jong Bo Park
Jung Nam An
Gaeun Bae
Kyu Hyeon Kim
Seong Joon Park
Youngjin Jung
Yong Chul Kim
Jung Pyo Lee
Jae Wook Lee
Dong Ki Kim
Yon Su Kim
Byung Hee Hong
Seung Hee Yang
author_facet Kyu Hong Kim
Jong Bo Park
Jung Nam An
Gaeun Bae
Kyu Hyeon Kim
Seong Joon Park
Youngjin Jung
Yong Chul Kim
Jung Pyo Lee
Jae Wook Lee
Dong Ki Kim
Yon Su Kim
Byung Hee Hong
Seung Hee Yang
author_sort Kyu Hong Kim
collection DOAJ
description 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.
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spelling doaj-art-c8fa20d2121c46ceb5cd3d07f2747b972025-08-20T02:23:12ZengWileyAdvanced Science2198-38442025-03-011210n/an/a10.1002/advs.202410747Effects of Graphene Quantum Dots on Renal Fibrosis Through Alleviating Oxidative Stress and Restoring Mitochondrial Membrane PotentialKyu Hong Kim0Jong Bo Park1Jung Nam An2Gaeun Bae3Kyu Hyeon Kim4Seong Joon Park5Youngjin Jung6Yong Chul Kim7Jung Pyo Lee8Jae Wook Lee9Dong Ki Kim10Yon Su Kim11Byung Hee Hong12Seung Hee Yang13Department of Biomedical Sciences Seoul National University Seoul South KoreaDepartment of Chemistry, College of Natural Sciences Seoul National University Seoul South KoreaDepartment of Internal Medicine Hallym University Sacred Heart Hospital Anyang South KoreaDepartment of Chemistry, College of Natural Sciences Seoul National University Seoul South KoreaDepartment of Biomedical Sciences Seoul National University Seoul South KoreaDepartment of Biomedical Sciences Seoul National University Seoul South KoreaDepartment of Chemistry, College of Natural Sciences Seoul National University Seoul South KoreaDepartment of Internal Medicine Seoul National University Hospital Seoul South KoreaDepartment of Internal Medicine Seoul National University Boramae Medical Center Seoul South KoreaNephrology Clinic National Cancer Center Goyang South KoreaDepartment of Internal Medicine Seoul National University Hospital Seoul South KoreaDepartment of Internal Medicine Seoul National University Hospital Seoul South KoreaDepartment of Chemistry, College of Natural Sciences Seoul National University Seoul South KoreaDepartment of Kidney Research Institute Seoul National University Medical Research Center Seoul South KoreaAbstract 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.https://doi.org/10.1002/advs.202410747TRPC5graphene quantum dotsmitochondrial membrane potentialoxidative stressrenal fibrosis
spellingShingle Kyu Hong Kim
Jong Bo Park
Jung Nam An
Gaeun Bae
Kyu Hyeon Kim
Seong Joon Park
Youngjin Jung
Yong Chul Kim
Jung Pyo Lee
Jae Wook Lee
Dong Ki Kim
Yon Su Kim
Byung Hee Hong
Seung Hee Yang
Effects of Graphene Quantum Dots on Renal Fibrosis Through Alleviating Oxidative Stress and Restoring Mitochondrial Membrane Potential
Advanced Science
TRPC5
graphene quantum dots
mitochondrial membrane potential
oxidative stress
renal fibrosis
title Effects of Graphene Quantum Dots on Renal Fibrosis Through Alleviating Oxidative Stress and Restoring Mitochondrial Membrane Potential
title_full Effects of Graphene Quantum Dots on Renal Fibrosis Through Alleviating Oxidative Stress and Restoring Mitochondrial Membrane Potential
title_fullStr Effects of Graphene Quantum Dots on Renal Fibrosis Through Alleviating Oxidative Stress and Restoring Mitochondrial Membrane Potential
title_full_unstemmed Effects of Graphene Quantum Dots on Renal Fibrosis Through Alleviating Oxidative Stress and Restoring Mitochondrial Membrane Potential
title_short Effects of Graphene Quantum Dots on Renal Fibrosis Through Alleviating Oxidative Stress and Restoring Mitochondrial Membrane Potential
title_sort effects of graphene quantum dots on renal fibrosis through alleviating oxidative stress and restoring mitochondrial membrane potential
topic TRPC5
graphene quantum dots
mitochondrial membrane potential
oxidative stress
renal fibrosis
url https://doi.org/10.1002/advs.202410747
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