# Panx1-PIEZO1 Interactions Regulate Renin Release

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $717,773

## Abstract

|| ABSTRACT
Hypertension is the most common pathological indicator for cardiovascular diseases. The key biological system
that regulates blood pressure is the renin-angiotensin-aldosterone system (RAAS); its dysregulation at almost
any level can precipitate hypertension. For this reason, pathways in the RAAS can be manipulated for
pharmacological interventions (e.g., ACE inhibitors). In this application we interrogate the release of renin, the
rate limiting step of activation of the RAAS, from juxtaglomerular (JG) cells in the afferent arterioles, and provide
exciting preliminary data to demonstrate a novel mechanically-sensitive signaling axis. In particular, the
application is focused on our recent work involving Panx1 channels in JG cells, and how they may be coupled
to the bona fide mechanically sensitive PIEZO1 channels specifically found in JG cells. Interestingly, we have
identified a role for estrogen receptor alpha that may provide a level of protection when coupled with PIEZO1.
Based on our preliminary data, we hypothesize renin release can be dictated by mechanically sensitive PIEZO-
Panx1 complexes in JG cells that are regulated by sex dependent and independent feedback. We propose three
aims to test this: 1. Protein kinase A (PKA) regulation of Panx1 channels; 2. changes in afferent arteriole
pressure is sensed by PIEZO1 and can regulate Panx1 and 3. estrogen receptor a regulates PIEZO channel
activity. In order to accomplish these aims, we have derived novel mouse lines (including Panx1T20A and Ren1D-
Cre/PIEZO1fl/fl) and state-of-the-art techniques (e.g., isolated renin secreting cells, isolated kidney perfusion,
calcium imaging on kidney slices). This application is composed of an internationally renowned team of experts,
with all proposed knockout mice being on hand, and robust preliminary data. We believe the data will provide an
important new layer of regulation in the RAAS capable of pharmacological intervention.

## Key facts

- **NIH application ID:** 10980409
- **Project number:** 1R01HL171997-01A1
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Brant E Isakson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $717,773
- **Award type:** 1
- **Project period:** 2024-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980409

## Citation

> US National Institutes of Health, RePORTER application 10980409, Panx1-PIEZO1 Interactions Regulate Renin Release (1R01HL171997-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10980409. Licensed CC0.

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