Kidney Week

Abstract: TH-PO0789

Proteins Involved in Mitochondrial Metabolism, Immune Response, and Inflammation Are Decreased in Npffr2-Deficient Mice Fed a Low-Salt Diet

Session Information

• CKM Axis: Vascular Dysfunction, Atherosclerosis, and Heart Failure in Kidney Diseases
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Cardiovascular-Kidney-Metabolic Health

• 601 Cardiovascular-Kidney-Metabolic Health: Basic

Authors

• Qaddumi, Waleed N., George Washington University School of Medicine & Health Sciences, Washington, District of Columbia, United States

Waleed N. Qaddumi, BS

• Polzin, Jacob Quentin Mullins, George Washington University School of Medicine & Health Sciences, Washington, District of Columbia, United States

Jacob Quentin Mullins Polzin

• Feranil, Jun, George Washington University School of Medicine & Health Sciences, Washington, District of Columbia, United States

Jun Feranil, MS, PhD, DVM

• Felder, Robin Allen, University of Virginia School of Medicine, Charlottesville, Virginia, United States

Robin Allen Felder, PhD

• Armando, Ines, George Washington University School of Medicine & Health Sciences, Washington, District of Columbia, United States

Ines Armando, MS, PhD

• Jose, Pedro A., George Washington University School of Medicine & Health Sciences, Washington, District of Columbia, United States

Pedro A. Jose, MD, PhD

• Lee, Hewang, George Washington University School of Medicine & Health Sciences, Washington, District of Columbia, United States

Hewang Lee, PhD

Background

The renal-selective infusion of neuropeptide FF (NPFF) increases systolic blood pressure (SBP) in mice. NPFFR1 and NPFFR2 are expressed in all nephron segments but NPFFR2 is expressed to a greater extent than NPFFR1. On normal salt (NS) (0.8% NaCl) diet SBPs are similar in Npffr2 wild-type (WT) and Npffr2 knockout (KO) mice. The effect of a low-salt (LS) (0.02-0.05% NaCl) or high salt (HS) (4% NaCl) diet on SBP in Npffr2 KO mice has not been reported.

Methods

Npffr2 KO and Npffr2 WT mice were sequentially fed for 14 days NS, HS, and LS diets. SBPs were measured by telemetry in conscious mice. At the end of the LS diet, the kidneys were harvested for proteomic analysis. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to identify the various signaling pathways are involved in BP regulation.

Results

In WT mice (n=3), the SBP (mm Hg) was increased by HS diet: (HS: 120±2, NS: 102±2). In KO mice (n=4) SBP was also increased by HS diet (HS: 110±1 vs NS: 98±2) but to a lesser extent than WT mice (KO: +12±3, WT: +19±2). Changing the diet from HS to LS decreased SBP to the levels observed on NS in both WT (106±3) and KO (100±3) mice. 181 proteins were downregulated and 24 proteins were upregulated in KO mice, relative to WT mice. DAVID analysis showed that proteins involved in mitochondrial metabolism (QCR10, NDUFAF1, NDUFB2, NDUFB3, COX5B) and proteins involved in immune responses and inflammation (IRAK1, MTOR, ECSIT, CTNND1, SCRIB, BRG1) were decreased in KO relative to WT mice whereas proteins involved in vesicular trafficking (SNX14, RAB3GAP2, EXOC4) were increased in KO relative to WT mice. Proteins involved in lipid metabolism were variably affected.

Conclusion

Suppression of mitochondrial metabolism and immune response may be adaptive mechanisms to maintain BP homeostasis in Npffr2 KO mice fed a low salt diet.

Acknowledgment

This work was supported by US National Institutes of Health grant R01DK134574.

Funding

• NIDDK Support