# Plasticity of renin cells in the kidney vasculature

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2020 · $561,067

## Abstract

Abstract 
Release of renin by juxtaglomerular cells usually suffices to maintain blood pressure and fluid-electrolyte
balance. However, if an adult mammal is subjected to manipulations that threaten homeostasis, smooth
muscle cells along the renal arterioles undergo a remarkable transformation: they switch from a contractile to
an endocrine phenotype acquiring the capacity to synthesize and release renin. Once homeostasis is
reestablished, the transformed cells become smooth muscle cells again. The ability to switch on and off the
renin phenotype seems to depend on the developmental history of the transformed cells: smooth muscle cells
descend from renin precursors and may retain the memory to synthesize renin when necessary to regain
homeostasis. Where in the genome the memory of the renin phenotype resides, how it is constructed,
and how it is retained or erased as the cells differentiate or change physiological status is unknown.
We observed that renin cells possess super-enhancers (SEs), dynamic clusters of large genomic regulatory
regions that are strong candidates to regulate the reenactment of the renin phenotype. Our overall
hypothesis is that the molecular memory of the renin phenotype resides in the chromatin state of the
arteriolar cells and is mediated by a distinctive set of SEs that control the identity of renin cells and
their descendants. Using in vivo and in vitro lineage tracking, reporters of gene activity, epigenome editing
and chromatin imaging techniques, we propose to pursue the following interrelated hypotheses and aims:
Aim 1. Test the hypothesis that acquisition of the renin cell phenotype is accompanied by the
establishment of unique SEs that enforce the expression of genes from the renin lineage.
Aim 2. Test the hypothesis that the renin SE regulates expression of the renin gene and through
dynamic chromatin interactions with other genes controls renin cell identity.
Understanding how vascular cells adopt and switch their identity is a fundamental biological question with
applicability to multiple, renal and extra renal diseases. This knowledge may lead to novel targets to prevent
renin cell fate changes that result in threatening cardiovascular, renal and hematopoietic diseases and inability
to coordinate multiple homeostatic responses. By providing essential new knowledge regarding the
mechanisms whereby arteriolar cells acquire and maintain their plasticity, a frontier basically unexplored, this
proposal has the potential to benefit children and adults with kidney and vascular diseases and hypertension.

## Key facts

- **NIH application ID:** 9897536
- **Project number:** 5R01DK116718-03
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** ROBERTO Ariel GOMEZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $561,067
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897536

## Citation

> US National Institutes of Health, RePORTER application 9897536, Plasticity of renin cells in the kidney vasculature (5R01DK116718-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9897536. Licensed CC0.

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