# Interaction of (pro)renin receptor and PPARy in regulation of plasma volume

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $575,533

## Abstract

Abstract
The collecting duct (CD), the terminal part of the nephron, plays a pivotal role in fine-tuning urinary water and
Na+ excretion to maintain homeostatic control of body fluid volume and blood pressure. This is the nephron site
where the transport processes are highly regulated by hormonal factors such as vasopressin and aldosterone.
Recently, we and others have discovered (pro)renin receptor (PRR) and PPARγ as important regulators of the
transport processes in the CD. In this regard, deletion of PRR in the nephron or the CD induces diabetes
insipidus and activation of PRR in the CD cells stimulates expression or activity of AQP2 and/or ENaC. The
action of PRR in the CD is mediated in part by releasing soluble PRR (sPRR). On the other hand, emerging
evidence shows that nuclear receptors play an important role in regulation of fluid balance beyond the energy
control. This is highlighted by the fluid-retaining action of PPARγ in the CD, which underlies thiazolidinedione-
induced fluid retention, a major off-target effect of the antidiabetic agents. In preliminary studies, we discovered
that site-1 protease (S1P) represents a predominant protease responsible for the cleavage process to produce
sPRR. Moreover, both PRR and S1P appear to be direct target genes of PPARγ in the CD. Based on these
observations, we hypothesize that PPARγ transcriptionally upregulates expression of PRR and S1P in the CD,
leading to enhancement of local sPRR production and activation of intrarenal RAS, ultimately increasing fluid
reabsorption and expanding plasma volume. To test this hypothesis, we propose the following 3 specific aims:
(1) to define PPARγ as a transcriptional activator of PRR gene in the CD cells, (2) to test the role of S1P-
derived sPRR in mediating Rosi-induced fluid retention, (3) to test the dependence of PRR/sPRR signaling
on binding to prorenin/renin during Rosi treatment. Together, new information resulted from this proposal is
expected to offer new insight into the newly discovered PRR-dependent pathway in the CD for homeostatic
control of fluid balance.

## Key facts

- **NIH application ID:** 9729034
- **Project number:** 5R01HL135851-03
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Tianxin Yang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $575,533
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9729034

## Citation

> US National Institutes of Health, RePORTER application 9729034, Interaction of (pro)renin receptor and PPARy in regulation of plasma volume (5R01HL135851-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9729034. Licensed CC0.

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