Abstract: TH-PO0108
Histone Deacetylase 11 Contributes to Septic AKI by Activation of EGFR/JAK2/STAT3 Signaling Pathway
Session Information
- AKI: Mechanisms - 1
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Shen, Fengchen, Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Du, Xinyu, Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Yu, Chao, Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Wang, Yanjin, Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Yao, Liyuan, Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Yu, Jianjun, Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Yan, Zhipeng, Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Zhuang, Shougang, Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
Background
Histone deacetylase 11 (HDAC11), the sole member of class IV HDACs, has been implicated in various tumors, metabolic disorders, and chronic diseases; however, its role in acute kidney injury (AKI) induced by sepsis remains largely unexplored. In this study, we investigated the role and mechanisms of HDAC11 in sepsis-induced AKI using a murine model.
Methods
A murine model of septic AKI was established through peritoneal administration of lipopolysaccharide (LPS) at a dosage of 10 mg/kg. Twenty-four hours post-LPS injection, blood and kidney tissues were collected for various analyses. These included assessment of renal function via serum creatinine and blood urea nitrogen (BUN) measurements, evaluation of kidney damage and HDAC11 expression through immunostaining/histochemistry, as well as analysis of renal tubular injury/apoptosis markers and phosphorylation status of signaling proteins via immunoblotting. HDAC11 was inhibited by FT895—a highly selective inhibitor of HDAC11 and global deletion of HDAC11 in mice.
Results
HDAC11 was found to be expressed in the cytosol of renal tubular cells and its levels increased in mice following LPS administration. This increase correlated with renal dysfunction characterized by elevated serum creatinine and BUN levels, alongside evidence of renal tubular cell injury/apoptosis indicated by heightened expression levels of Ngal, cleaved-caspase 3, Bax, and p53. Treatment with FT895 resulted in improved renal function, reduced kidney damage, and diminished apoptosis. Global deletion of HDAC11 yielded similar outcomes. Additionally, LPS injection led to increased phosphorylation levels of epidermal growth factor receptor (EGFR), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (Stat3) within the kidneys; these effects were suppressed either by FT895 treatment or genetic deletion of HDAC11.
Conclusion
The data suggest that HDAC11 plays a critical role in the development of AKI through mechanisms associated with the activation of the EGFR/JAK2/STAT3 signaling pathway.
Funding
- Government Support – Non-U.S.