Abstract: TH-PO0124
Renal Sympathetic Nerve Stimulation Attenuates Sepsis-Induced AKI via Tubular β2-Adrenergic Receptors and Metallothionein Induction
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
- Shimoyama, Kotaro, Nagasaki Daigaku, Nagasaki, Nagasaki Prefecture, Japan
- Umene, Ryusuke, Nagasaki Daigaku, Nagasaki, Nagasaki Prefecture, Japan
- Wu, Chia-Hsien, Nagasaki Daigaku, Nagasaki, Nagasaki Prefecture, Japan
- Nakamura, Yasuna, Nagasaki Daigaku, Nagasaki, Nagasaki Prefecture, Japan
- Inoue, Tsuyoshi, Nagasaki Daigaku, Nagasaki, Nagasaki Prefecture, Japan
Background
Sympathetic hyperactivity is commonly observed during sepsis due to hypotension, and adrenergic agents are frequently used to support hemodynamics. However, the role of renal sympathetic nerve activity (RSNA) in sepsis-associated acute kidney injury (AKI) remains poorly understood. This study used an optogenetic approach to selectively stimulate renal sympathetic nerves and evaluate their role in septic AKI.
Methods
DbHCre-ChR2 mice expressing channelrhodopsin-2 in peripheral noradrenergic neurons were used. Bilateral renal sympathetic nerves were stimulated with 20 Hz blue LED pulses for 5 minutes. Twenty-four hours later, sepsis was induced by intraperitoneal lipopolysaccharide (LPS, 5 mg/kg) injection. Renal function and injury markers were evaluated 24 hours post-LPS. Adrenergic receptor subtypes were localized by immunostaining. β2-adrenergic receptor (β2-AR) function was examined using the β2-AR agonist salbutamol and β2-AR tubule-specific knockout mice (SGLT2-Cre:β2-ARflox). HK-2 cells were treated with LPS ± salbutamol to assess NGAL expression. RNA sequencing was performed to identify downstream mediators.
Results
Renal sympathetic stimulation significantly suppressed LPS-induced increases in plasma creatinine, BUN, and renal Ngal and Kim-1 expression. Among adrenergic receptor subtypes, only β2-AR was expressed in renal tubules. Salbutamol administration replicated the renoprotective effect of nerve stimulation, while β2-AR deletion in tubular cells abolished this protection. In HK-2 cells, salbutamol reduced LPS-induced NGAL expression in a dose-dependent manner. RNA sequencing identified upregulation of metallothionein 1, a zinc-regulated antioxidant gene, which also conferred renal protection when overexpressed.
Conclusion
Selective renal sympathetic nerve stimulation protects against septic AKI by activating tubular β2-adrenergic receptors and inducing metallothionein. These findings reveal a novel neuro-renal axis involving adrenergic signaling and antioxidant defense.