# Role of (pro)renin receptor in aldosterone signaling in the kidney

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $528,448

## Abstract

(Pro)renin receptor (PRR) binds prorenin/renin in vitro to increase their catalytic activity and
therefore is postulated to be a regulator of renin. Soluble PRR (sPRR) residing in the
extracellular domain of PRR is produced by furin or ADAM19-dependent cleavage process and
has been widely studied as a disease biomarker. Although PRR has an established role in
embryogenesis in both low vertebrates and mammals, the potential role of PRR/sPRR in
regulation of mammalian renal function and blood pressure largely remains elusive. Within the
kidney, PRR is predominately expressed in the distal nephron, particularly the intercalated cells
of the collecting duct (CD). In preliminary studies, we discovered a previously undescribed
paracrine action of PRR/sPRR with intercalated cell-derived sPRR acting on principal cells to
stimulate ENaC-mediated Na+ reabsorption. We presented further evidence that PRR/sPRR-
mediated paracrine control of Na+ transport contributes to pathogenesis of mineralocorticoid-salt
hypertension. This proposal will test the overall hypothesis that during mineralocorticoid excess,
the expression of PRR/sPRR is increased in the distal nephron where sPRR binds Frizzled-8 to
activate β-catenin signaling that activates adenylyl cyclase-3 (AC3)/cAMP/PKA pathway that
stimulates ENaC transcription and activity and hence hypertension and kidney injury. To test this
hypothesis, we will employ conditional gene targeting techniques to evaluate the contribution of
CD PRR and β-catenin to ENaC activation and hypertension. Moreover, we will dissect sPRR-
induced signaling mechanisms involving coordinated activation of Frizzled-8/β-catenin and
AC3/cAMP/PKA pathways in the CD cells. Lastly, we will explore a novel therapeutic potential
of inhibitors of β-catenin signaling in mineralocorticoid-salt hypertension. Overall, this proposal
is expected to offer novel insight into the function of renal PRR/sPRR in hypertension and
kidney injury.

## Key facts

- **NIH application ID:** 9921471
- **Project number:** 5R01HL139689-03
- **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:** $528,448
- **Award type:** 5
- **Project period:** 2018-06-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9921471

## Citation

> US National Institutes of Health, RePORTER application 9921471, Role of (pro)renin receptor in aldosterone signaling in the kidney (5R01HL139689-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9921471. Licensed CC0.

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