Abstract: SA-PO0246
HDAC3 Plays a Crucial Role in Cisplatin-Induced Tubular Cell Necrosis and AKI
Session Information
- AKI: Mechanisms - Cell Signaling
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Dong, Guie, Augusta University Medical College of Georgia, Augusta, Georgia, United States
- Dong, Zheng, Augusta University Medical College of Georgia, Augusta, Georgia, United States
Background
Cisplatin is a chemotherapy drug that is used to treat various cancers, but it causes damage to normal tissues or organs, especially to the kidney. Histone deacetylases (HDAC) are a class of enzymes that remove acetyl groups from lysine residuals on both histone and non-histone proteins, leading to epigenetic regulation. In this study, we investigated the role of HDAC3 in cisplatin-induced acute kidney injury (AKI) with a focus on tubular cell necrosis.
Methods
In vitro, mouse kidney proximal tubular (BUMPT) cells were treated with high dose (1mM) cisplatin to induce necrosis. In vivo, mice were injected with 30 mg/kg cisplatin to induce AKI. The role of HDAC3 was examined by using its pharmacological inhibitor RGFP966 or by genetic ablation of HDAC3 from kidney proximal tubules.
Results
Cisplatin induced significantly necrosis in BUMPT cells as shown by propidium iodide (PI) staining and lactate dehydrogenase (LDH) release, which was suppressed by RGFP966. RGFP966 also preserved histone acetylation during cisplatin treatment. To examine the role of HDAC3 in vivo, we generated a conditional knockout mouse model in which HDAC3 was specifically ablated from kidney proximal tubule cells (PT-HDAC3-ko). Compared with wild-type mice, PT-HDAC3-ko mice had less tubular injury after cisplatin treatment. Consistently, PT-HDAC3 mice showed lower levels of serum creatine and blood urea nitrogen (BUN). Histone deacetylation observed during cisplatin treatment was also suppressed in PT-HDAC3 mice kidney tissues.
Conclusion
Inhibition of HDAC3 pharmacologically or genetically protected the kidney from cisplatin nephrotoxicity, including tubular necrosis. The results suggest HDAC3 as a potential therapeutic target for kidney protection in cancer patients undergoing cisplatin treatment.
Acknowledgment
The work was supported by the National Institutes of Health (DK087843, DK142969) and Veteran’s Administration (I01BX000319, IK6BX005236)
Funding
- NIDDK Support