Abstract: TH-PO0025
Dipeptidyl Peptidase 4 Modulates Proximal Tubule Sodium/Hydrogen Exchanger-Mediated Sodium Reabsorption by Altering Its Apical Microvillar Membrane Localization
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Basic Research
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic
Authors
- Ben Musa, Ruwaida, University of Missouri, Columbia, Missouri, United States
- Nistala, Ravi, University of Missouri, Columbia, Missouri, United States
Background
Salt-sensitive hypertension (SS-HT) is characterized by increases in blood pressure in response to high salt intake and corresponding reductions with salt restriction. Dysregulated renal sodium reabsorption within the proximal tubule (PT), is a major determinant of salt sensitivity. The sodium–hydrogen exchanger 3 (NHE3) is the dominant sodium transporter in the PT and plays a central role in controlling tubular sodium reabsorption. Modulation of NHE3 activity therefore represents an important therapeutic strategy for improving SSHT. Previous studies have shown that NHE3 function is regulated through various mechanisms, including DNA methylation, phosphorylation, protein–protein interactions, and dynamic membrane localization. In this regard, dipeptidyl peptidase-4 (DPP4), a type II transmembrane glycoprotein that is highly enriched in the PT brush border, binds to NHE3 and inhibits sodium uptake in vitro, may regulate NHE3 function under salt sensitive conditions.
Methods
Aged male and female Dpp4 wild-type (DPP4WT) and Dpp4 knockout (DPP4KO) mice were housed in metabolic cages for 4-8 days and fed a high salt (1.2%, HS), normal salt (0.2%, NS) or a low salt (0.02%) diet. Daily sodium intake and excretion were measured and sodium balances were calculated. Immunofluorescence statining was performed on kidney tissue sections using PLP fixative and antibodies
against NHE3 (Bicell, St. Loius MO; Cat. #21003) and DPP4 (R&D systems, Minneapolis, MN; Cat. #AF954). BP measurement was done using tail-cuff plethysmography (Kent Scientific, Torrington, CT, Cat. #CODA-HT2).
Results
DPP4KO mice exhibited higher sodium excretion when compared to DPP4WT mice under both LS & HS conditions leading to a better sodium balance. DPP4KO mice had reduction in membrane localization of NHE3 in both NS and HS conditions, while the DPP4WT mice had lower apical membrane localization of NHE3 in HS compared to NS conditions. Aged female mice were more salt sensitive (higher BP) compared to male mice and this was true for both DPP4WT and DPP4KO. Higher salt sensitivity in female mice was associated with higher NHE3 apical membrane localization.
Conclusion
DPP4 regulates PT sodium handling. This regulation maybe largely attributable to modulation of NHE3 apical membrane localization. Targeting DPP4-NHE3 axis may represent a RAAS-independent strategy to treat SS-HT.
Acknowledgment
We acknowledge NIH/NIDDK, FAPESP (Brazil) and the University of Missouri School of Medicine, Columbia for their support and provision of resources.
Funding
- NIDDK Support