# A Novel Approach to Aldosterone Signaling

> **NIH NIH F30** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $44,190

## Abstract

Project Summary
Aldosterone, a steroid hormone produced by the adrenal glomerulosa, plays a significant role in the
pathophysiology of cardiovascular disease. Drugs that block aldosterone signaling are central to modern
cardiovascular medicine; however, side effects restrict their use. Our understanding of aldosterone signaling at
the molecular level is incomplete, limiting the development of new approaches to block aldosterone signaling.
Aldosterone acts via the mineralocorticoid receptor (MR) to regulate transcription of genes encoding aldosterone-
induced proteins. In the collecting ducts of the kidney, these proteins regulate activity of the epithelial sodium
channel ENaC, resulting in increased channel activity and sodium retention. A number of aldosterone-induced
proteins have been identified using cell culture models; however, deletion of these proteins in mice does not
produce the expected phenotype of renal sodium wasting, elevated plasma potassium, and low blood pressure
observed in mice with deletion of the MR specifically in the kidney epithelium (KS-MR-/- mice). Thus, aldosterone-
induced proteins essential for activation of ENaC remain to be identified. This proposal seeks to identify these
proteins using a novel approach that overcomes the limitations of previous screens. Specifically, this will be
achieved by taking an in vivo approach that compares the transcriptional response to dietary sodium restriction,
which stimulates endogenous aldosterone, in the collecting ducts of KS-MR-/- and control mice. Proteins encoded
by transcripts that are induced in the control mice but not in the KS-MR-/- mice will be considered candidate
proteins which will be further tested for aldosterone-dependence by Western blot and immunofluorescence. To
determine whether candidate proteins modulate ENaC activity, amiloride-sensitive transepithelial current (a
measurement for ENaC activity) will be determined in mouse kidney epithelial cells following siRNA knockdown
of each candidate protein. The specific aims of this proposal are: (1) to identify novel aldosterone-induced
proteins in the collecting duct and (2) to examine the role of aldosterone-induced proteins in activation of ENaC.
This work will improve our understanding of aldosterone signaling and regulation of ENaC activity.

## Key facts

- **NIH application ID:** 9952367
- **Project number:** 5F30DK114980-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Elizabeth Anne Swanson
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $44,190
- **Award type:** 5
- **Project period:** 2018-07-01 → 2021-03-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952367

## Citation

> US National Institutes of Health, RePORTER application 9952367, A Novel Approach to Aldosterone Signaling (5F30DK114980-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9952367. Licensed CC0.

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