Abstract: PO2477
Graphene Quantum Dots Protects Against Renal Fibrosis After Restoring Mitochondria Function in Rat 5/6 Nephrectomy
Session Information
- CKD: Inflammation, Endothelial Dysfunction, and Signaling
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Kim, Kyu hong, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
- Kwon, Soie, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
- Cho, Semin, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
- Yoo, Kyung Don, Ulsan University Hospital, Ulsan, Korea (the Republic of)
- Kim, Yong Chul, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
- Lee, Jae Wook, National Cancer Center, Goyang, Gyeonggi-do, Korea (the Republic of)
- Kim, Dong Ki, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
- Kim, Yon Su, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
- Yang, Seung Hee, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
Background
Graphene Quantum Dots (GQDs) are carbon-based nanoparticles and spotlighted in biological application due to their biocompatibility, quantum confinement and low toxicity. Rat with subtotal 5/6 nephrectomy exhibit mitochondrial dysfunction mediated by TRPC5 channel, a core calcium channel in podocytes and tubular cells. With current limited understanding of the interaction on between nanomaterials and renal cells, we show GQDs as a potential therapeutic nano-sized material in 5/6 nephrectomy rat model.
Methods
To evaluate GQDs therapeutic effect on 5/6 nephrectomy Sprague Dawley (8-week; male) rat model, GQDs (4mg/kg) was administered by intraperitoneal for 3 times per week up to 8 weeks. In vitro stimulation, recombinant TGF-beta (2mg/mL) was treated in both human primary podocytes and tubular cells with GQDs in dose-dependent manner (0.1ug/mL, 0.5ug/mL, 1ug/mL). Renoprotection in 5/6 nephrectomy were assessed through combination of flow cytometry, Annexin V – FTIC Apoptosis staining, histomorphometry, functional manipulations, protein and mRNA expressions. Intracellular Calcium permeability was measured from Fura 2-AM.
Results
GQDs pivotal role in 5/6 nephrectomy led to identification of the partial proteinuria recovery and antihypertensive effects. In Vivo study discloses GQDs anti-fibrosis role as impeding MMT process that co-express macrophage (CD68) and myofibroblast (a-SMA). Thus, in vitro study after TGF-beta induction show similar results. GQDs-treated group in rats have increased potential cell viability by downregulating the cyclin kinase inhibitors after decreasing Bax-2, P53, P21 but increasing BCL2 expression. Next, Annexin staining result shows GQDs-treated group have a higher viable cells population (-/-) than 5/6 nephrectomy. Computing differential gene expression (DGE), RNA sequencing (RNA-seq) highlights the significant folding changes in TRPC5 gene from GQDs-treated group. Acute stimulation of calcium movement measured by Fura 2-AM was lowered in GQDs group and TRPC5 protein function expression. Interestingly, after TRPC5 modulation by GQDs, mitochondrial dysfunction is repaired.
Conclusion
GQDs restores mitochondrial function associated with TRPC5 activation pathways. This gratitude of GQDs for renal preservation will promote next generation of CKD treatments.