# (Pro)renin receptor mediates obesity induced hypertension

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2020 · $363,375

## Abstract

Hypertension is a common and morbid complication of obesity. The pathophysiologic mechanisms involved in
obesity-induced hypertension are not well elucidated. In this application we propose that (Pro)renin receptor
(PRR), a newly discovered receptor, plays a major role in the development of obesity associated hypertension.
Recent studies confirmed presence of this receptor in adipose tissue and kidneys. The lack of PRR specific
antagonists and the lethality of its total deletion, made it difficult to study this receptor. Currently, the
contribution of PRR to development of obesity-induced hypertension is unknown. In order to study PRR in
adipose tissue and the kidney, this proposal will utilize two novel mouse models namely the inducible
adipocyte specific PRR knockout mouse and the inducible nephron specific PRR knockout mouse. Our
preliminary data demonstrated that obese mice developed hypertension with increased PRR expression and
production of proinflammatory cytokines in adipose tissue and kidneys. These data also suggested that PRR
regulates ENaC expression in the kidney. Based on these data, we propose that PRR contributes to
development of obesity-induced hypertension by enhancing sodium retention. The long-term goal of our
research program is to elucidate the novel mechanisms contributing to the regulation of PRR expression and
function and evaluate its interaction with proinflammatory cytokines, angiotensin subtype AT1 receptor (AT1R),
and ENaC in development of obesity-induced inflammation and hypertension. To achieve this goal, we will
utilize a rationale and novel integrated approaches, including in vitro state-of-the-art cellular and molecular
techniques, in vivo studies utilizing two novel inducible tissue specific PRR knockout mouse models, Laser
Scanning Confocal FRET microscopy and in vivo microdialysis, to rigorously test the proposed hypothesis.
Based on our preliminary data, the central hypothesis of this proposal is that PRR contributes to the
development of obesity-induced hypertension via enhancing adipose tissue and kidney inflammation
and PRR-AT1R dimer formation, leading to increased renal ENaC activity and sodium retention. We
will pursue the following integrated specific aims:
Specific Aim I: To test the hypothesis that adipocyte PRR contributes to the development of obesity-induced
hypertension via enhancing adipocyte IL-1, IL-6, TNFα-renal ENaC pathway.
Specific Aim II: To test the hypothesis that the nephron PRR contributes to the development of obesity-
induced hypertension via enhancing PI3K-AKT-mTOR-SGK1-Nedd4-2-α-ENaC pathway.
Specific Aim III: To test the hypothesis that PRR forms a heterodimer with angiotensin AT1R to enhance
development of obesity-induced hypertension, via ERK-NFB-proinflammatory cytokines-αENaC pathway.
These studies will identify novel pathophysiologic mechanisms related to obesity-induced hypertension and
could lead to the development of new therapeutic strategies in treating this co...

## Key facts

- **NIH application ID:** 9944627
- **Project number:** 5R01DK114875-04
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Helmy M Siragy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $363,375
- **Award type:** 5
- **Project period:** 2017-08-17 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944627

## Citation

> US National Institutes of Health, RePORTER application 9944627, (Pro)renin receptor mediates obesity induced hypertension (5R01DK114875-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9944627. Licensed CC0.

---

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