Graphene Quantum Dots Prevent Glomerular and Interstitial Injury in Murine Adriamycin Nephropathy Through Macrophage Depletion
1Internal Medicine, Seoul National University Hospital, Seoul, Korea, Republic of, 2Internal Medicine, Nephrology Clinic, National Cancer Center, Seoul, Korea, Republic of
Meeting: 2020 American Transplant Congress
Abstract number: D-372
Keywords: Apoptosis, Fibrosis, Inflammation, Kidney
Session Information
Date: Saturday, May 30, 2020
Session Name: Poster Session D: Innate Immunity; Chemokines, Cytokines, Complement
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
Location: Virtual
*Purpose: Macrophage infilatration is a key feature of the pathogenicity associated with glomerular and tubulo-interstitial injury in kidney disease. Graphene quantum dots (GQDs) are considered a promising material because of their good free radical scavenging activity, low toxicity, and excellent water solubility. Here, to investigate this possibility, the effect of GQDs was studied in a murine model (adriamycin nephropathy)
*Methods: In this study, to investigate the effect of GQDs on renal injury, we used Adriamycin nephropathy mice model and H2O2-induced in vitro models with cultured human podocytes. Adriamycin nephropathy was produced in male BALB/c mice by a single intravenous injection of adriamycin (11.5 mg/kg). GQDs were given by intraperitoneal at days -1, 0, 1, and 4. After seven weeks, renal function and histology were studied by histomorphometry, immunohistochemistry, and flow cytometry.
*Results: Compared with control-treated mice, GQDs-treated mice also restored kidney function and decreased proteinuria and pathologically decreased mesangial expansion, glomerular sclerosis, and interstitial expansion than the mice on Adriamycin alone. The administration of GQDs significantly reduced not only NGAL expression, but also pSTAT3 expression in the kidney. In vitro stimulation of primary cultured podocytes with H2O2, GQDs-mediated renal protection was associated with reduced IL-11, IL-18, reactive oxygen species (ROS) and the proportion of dead cells. Flow cytometric analysis showed a marked decrease in the number of CD11b+Gr1+CD206+ macrophage in kidney and spleen of the GQDs-treated mice. Microarray analysis highlights a cascade of specific gene expression patterns related to apoptosis, cell cycle, kidney injury, especially DNA damage repose pathways such as Parp9, Parp10, Mad2l2 and Ap5s1.
*Conclusions: Our study has uncovered a major protective role of GQDs in AD model through macrophage depletion. GQDs is a potential therapeutic target for renal preservation.
To cite this abstract in AMA style:
Kim Y, Kim K, Lee J, Moon J, Kim J, Lee J, Kim Y, Yang S. Graphene Quantum Dots Prevent Glomerular and Interstitial Injury in Murine Adriamycin Nephropathy Through Macrophage Depletion [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/graphene-quantum-dots-prevent-glomerular-and-interstitial-injury-in-murine-adriamycin-nephropathy-through-macrophage-depletion/. Accessed September 29, 2020.« Back to 2020 American Transplant Congress