Abstract: TH-PO0149
Recombinant Na-H Exchanger Regulatory Factor 1 (NHERF1) Prevents Kidney Injury
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
- Lederer, Eleanor D., The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Gaweda, Adam E., University of Louisville School of Medicine, Louisville, Kentucky, United States
- Gagnon, Kenneth Bradley, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Rane, Madhavi J., University of Louisville School of Medicine, Louisville, Kentucky, United States
Background
We have shown that NHERF1 knock out mice are more susceptible than wild type (WT) mice to cisplatin-induced acute kidney injury (CIS-AKI). We have also shown increased apical membrane expression of NHERF1 in WT mice after CIS-AKI, suggesting a role for NHERF1 in the response to AKI. We hypothesized that administration of recombinant NHERF1 (rmNHERF1) to knock out mice would prevent AKI.
Methods
4 month old NHERF1fl/fl;Npt2aCreERT2 C57Bl6J mice received 5 intraperitoneal (IP) tamoxifen [50mg/kg] injections followed by 14-day washout to abolish proximal tubule (PT) NHERF1 expression. They underwent tail-vein injection of rmNHERF1 24 h prior to IP injection of CIS [20mg/kg], followed by sacrifice 72 hours after CIS. 12 randomly chosen fields from paraffin-embedded kidney cortex slices from 2 mice were imaged by confocal microscopy for immunofluorescent expression of rmNHERF1, Kidney Injury Molecule 1 (KIM1), and Lotus tetragonobolus to identify PTs (LTL+). For each PT, rmNHERF1 and KIM1 staining were recorded as categorical variables. The distribution of rmNHERF1 and KIM1 expression was analyzed by Chi-Square and Fisher's Exact test.
Results
We identified total of 255 LTL+ PTs from 12 fields. Recombinant rmNHERF1 localized to and was stably expressed in PT for 96h post injection. The majority of the PTs expressed rmNHERF1. 167 PTs expressed rmNHERF1 but not KIM1. 65 expressed KIM1 but not rmNHERF1. 23 PTs expressed both rmNHERF1 and KIM1. No LTL+ PTs lacked both rmNHERF1 and KIM1 staining. (See Figure) Chi-square analysis showed highly significant variance by Chi-square with Fisher Exact t test (p < 0.0001).
Conclusion
These results suggest that successful expression of exogenous rmNHERF1 prevents CIS-AKI. Investigation into the mechanism and therapeutic potential of NHERF1 in the prevention and treatment of AKI is warranted.
Funding
- Veterans Affairs Support