# Renin cell identity and blood pressure homeostasis

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2020 · $685,695

## Abstract

PROJECT SUMMARY/ABSTRACT
The renin-angiotensin system (RAS) is crucial in the regulation of the blood pressure (BP). Synthesis and
secretion of renin is the key regulated event in the operation of the RAS. One of the main mechanisms that
control renin synthesis and release is the baroreceptor mechanism whereby a decrease in BP results in
increased release of renin by juxtaglomerular (JG) cells. Under normal circumstances, secretion of renin by JG
cells is sufficient to balance transient changes in BP. However, if the drop in renal perfusion pressure is
protracted, additional cells along the renal arterioles are transformed to the renin phenotype to meet the
perceived demands for renin and regain homeostasis. In spite of its enormous importance, the nature and
location of the renal baroreceptor, and whether mechanical signals are transmitted directly to the renin cell
nucleus to activate Renin gene expression is still unknown. It has been assumed that this pressure sensing
mechanism is located at the afferent arterioles either in the JG cells or the vascular smooth muscle cells (SMCs)
upstream from them. Recent studies from our laboratory identified a unique set of super-enhancers (SEs) that
determine the identity of renin cells, in which the Renin SE ranked the highest. External mechanical forces may
trigger changes in nuclear envelope structure, chromatin organization and gene expression. We hypothesize
that JG cells and/or their descendants sense variations in perfusion pressure and respond to them with marked
and unique changes in chromatin configuration resulting in changes in Renin gene expression and in the case
of SMCs the adoption of the renin phenotype via the assembly of a Renin SE. We further hypothesize that this
pressure sensing mechanism is a nuclear mechanotransduction process whereby extracellular physical forces
are transmitted directly to the chromatin to regulate Renin gene expression, renin bioavailability and cell identity.
Whether the same set of SEs or a different set is activated in response to changes in perfusion pressure is
unknown. Using multiple approaches, well established in our laboratories, including genetically modified mice,
cell lineage tracing, in vivo high and low perfusion pressure models, epigenomic analysis and editing, and in vitro
imaging of chromatin dynamics, we will test the following hypotheses: Aim 1: Changes in perfusion pressure
sensed by renin cells and/or their descendants result in unique and specific changes in chromatin architecture
which in turn control the expression of Renin and the identity of renin cells, Aim 2: Integrin β1 controls renin cell
identity via chromatin architectural changes and SE formation, and Aim 3: Lamin A/C regulates chromatin
remodeling and the formation of SEs in renin cells in response to changes in arterial pressure in vivo and
mechanical deformation in vitro. This research is crucial to understand how BP homeostasis is maintained in
health and disease. Knowledge g...

## Key facts

- **NIH application ID:** 9971973
- **Project number:** 1R01HL148044-01A1
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** MARIA LUISA Soledad SEQUEIRA-LOPEZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $685,695
- **Award type:** 1
- **Project period:** 2020-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971973

## Citation

> US National Institutes of Health, RePORTER application 9971973, Renin cell identity and blood pressure homeostasis (1R01HL148044-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9971973. Licensed CC0.

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