Abstract: SA-PO0245
Determining the Effect of Cholinergic Agonists on Murine 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
- Chiramel, Rachel, Liberty University, Lynchburg, Virginia, United States
- Smith, Tavin, Liberty University, Lynchburg, Virginia, United States
- Gigliotti, Joseph C., Liberty University, Lynchburg, Virginia, United States
Background
Acute kidney injury (AKI) is a significant healthcare burden worldwide and the immune system mediates the pathogenesis of AKI in mice. Previous work suggests that cholinergic agonists are potential treatment options, however the data has been contradictory. We set out to verify the utility of cholinergic agonists in preventing AKI in mice and if these outcomes are influenced by disease severity.
Methods
Studies were performed in accordance with the Liberty University IACUC. Male C57Bl/6 mice underwent unilateral renal ischemia reperfusion injury (IRI). Injury severity was modified by clamping the renal pedicle for 20, 25, or 30 minutes to model mild, moderate, and severe AKI, respectively. Nicotine (NIC, 1mg/kg), the alpha-7 cholinergic receptor agonist GTS-21 (4mg/kg), or saline vehicle were administered IP 90 minutes before ischemia. Mice were euthanized 24 hours post-IRI, and ischemic kidneys harvested for histology and mRNA expression of Il-6, Kim1, Krt20, Atf3, and Top2a by RT-PCR. Renal hemodynamics were estimated using Doppler ultrasound 90 minutes after the administration of NIC, GTS-21, or vehicle. Renal mRNA expression of the fibrotic markers Acta2, Tgfb1, Col1a, Col3a, and Vim, were also quantified 4 weeks after AKI. Data were analyzed using GLM Procedures in SPSS and results were considered significant if P<0.05.
Results
IRI severity was confirmed by acute tubular necrosis (ATN) and renal Kim1 (P=0.01) and Top2a (P=0.007) mRNA expression. At moderate severity, GTS-21 upregulated the expression of pro-inflammatory and injury-related genes Il6 (P=0.002), Kim1 (P<0.001), and Krt20 (P=0.04) compared to NIC. Reparative Top2a expression was also reduced in the NIC group compared to vehicle at moderate severity (P=0.008). NIC administration lowered Kim1 expression in severe AKI as compared to mice treated with vehicle (P=0.04). Despite these molecular findings, cholinergic agonists did not influence ATN regardless of injury severity. No differences in fibrosis related genes were observed 4 weeks after AKI. The administration of NIC or GTS-21 caused a >50% reduction (P<0.02) in peak systolic velocity in the renal artery as compared to vehicle.
Conclusion
Our data suggest that cholinergic agonists influence key molecular pathways in AKI in a severity-dependent manner. However, there does not appear to be an overall improvement in ATN and fibrosis with cholinergic agonists and this could be due to altered renal hemodynamics.