# The role of salt and SGK1 on NADPH oxidase stabilization in dendritic cells in hypertension

> **NIH NIH F32** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $59,161

## Abstract

PROJECT SUMMARY
Hypertension is the leading cause of morbidity and mortality from stroke, myocardial infarction, heart
failure, and chronic kidney disease. Despite the importance of blood pressure control, the pathogenesis
of essential hypertension remains poorly understood. In the past several years it has become clear that
sodium can accumulate in the interstitium, particularly in the skin and skeletal muscle and that these
modestly elevated concentrations of sodium can drive immune cell activation. Our laboratory has
recently described a new pathway by which extracellular sodium activates NADPH oxidase in dendritic
cells and showed that this promotes isolevuglandin-adducts that are recognized as non-self and evoke
an immune response. I propose that salt stabilizes NADPH oxidase subunits, specifically p22phox, via
serum and glucocorticoid-regulated kinase 1 (SGK1) in dendritic cells (DCs), which leads to the
promotion of hypertension. In Aim 1, I will test the hypothesis that stabilization of p22phox protein in
response to salt is dependent on SGK1 and to determine if this promotes DC activation and
hypertension. In this aim I will use mice in which we have deleted SGK1 specifically in DCs. In the first
part of this aim, I will demonstrate if this increased sodium indeed enhances stability of the NADPH
oxidase protein subunits and if this is dependent on SGK1. In a second series of experiments, I will
examine the effect of SGK1 on the phenotype of DCs. DCs will be analyzed by flow cytometry and for
superoxide production by electron spin resonance. In additional experiments, I will examine the in vivo
role of SGK1 in DCs. I will perform adoptive transfer of dendritic cells co-treated with mannitol or high
salt into naïve mice and measure blood pressure by radiotelemetry. I predict that deletion of SGK1
prevents NADPH oxidase subunit stabilization, production of superoxide, and increase is blood
pressure with low dose angiotensin II. In aim 2, I will determine if NADPH oxidase subunits p22phox,
p47phox, and/or gp91phox are ubiquitinated in response to salt via SGK1, and to determine if this
promotes DC activation and hypertension. In these studies, we will perform immunoprecipitation of the
NADPH oxidase subunits p22phox, p47phox and gp91phox. We will use mass spectrometry to identify
ubiquitinated lysines of the NADPH oxidase subunits. In additional experiments, we will assess p22phox,
p47phox, and gp91phox ubiquitination in vivo utilizing a rodent model of salt-sensitive hypertension. I
predict that NADPH oxidase subunits will be stabilized during high salt treatment, and that genetic
deletion of SGK1 will prevent this in DCs. This will advance our understanding of hypertension and will
provide new therapeutic directions for this disease.

## Key facts

- **NIH application ID:** 10063425
- **Project number:** 5F32HL143927-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Justin Pieter Van Beusecum
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $59,161
- **Award type:** 5
- **Project period:** 2019-05-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10063425

## Citation

> US National Institutes of Health, RePORTER application 10063425, The role of salt and SGK1 on NADPH oxidase stabilization in dendritic cells in hypertension (5F32HL143927-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10063425. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*