Abstract: SA-PO166
Functioning and Molecular Mechanism of Histone Lactylation in AKI
Session Information
- AKI: Mechanisms - III
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Author
- Liu, Zhenzhen, Shandong First Medical University, Jinan, Shandong, China
Group or Team Name
- Xinwei Research Group.
Background
Acute kidney injury (AKI) is a common clinical problem, which is defined as the abrupt deterioration of kidney function that results in a decreased glomerular filtration rate. Studies have demonstrated that AKI is associated with a reduced survival rate of patients, increased incidence of chronic kidney disease (CKD), and other complications.
Methods
Although lactylation has been widely studied in the context of cancer, inflammation, and regeneration, its role in AKI remains poorly understood. To address this gap, we conducted a comprehensive investigation into the effects and mechanisms of lactylation in ischemic AKI, utilizing flow cytometry, Western blot, PCR, immunofluorescence, Seahorse in vivo and in vitro.
Results
Our findings demonstrated that pan-lactylation and H3K18 lactylation were significantly reduced in tubular epithelial cells (HK-2 cells) and renal tissue under ischemia in vitro and in vivo. Interestingly, we found that ING2 expression were significantly reduced under ischemia and overexpression of ING2 could inhibit apoptosis of HK-2 cells . In mechanism,ING2 knockout or overexpression could regulate lactylation. Finally, ING2 could regulate lactylation through p300 and promoting histone lactylation could reverse ischemia-induced HK-2 cells injury and ischemia-reperfusion induced AKI in mice.
Conclusion
These results suggested that a unrecognized role of lactylation in kidney injury and a promising target for therapeutic intervention of AKI.