# Regulatory RNA in Hypertension

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2022 · $385,000

## Abstract

PROJECT SUMMARY
 More than 50% of hypertensive patients show an increased blood pressure sensitivity to salt intake.
However, population-wide reduction of salt intake has proved to be difficult, making it ever more important to
better understand the mechanism of salt-sensitive hypertension and provide a basis for developing new
interventions. The kidney plays a key physiological role in the development of hypertension including salt-
sensitive hypertension.
 Thousands of genes in the genome encode long non-coding RNAs (lncRNAs). lncRNAs can interact
with and influence the function of other RNA or proteins. Few lncRNAs have been studied for their role in
hypertension. Unlike most lncRNAs, MALAT1 (metastasis associated lung adenocarcinoma transcript 1; Malat1
in rodents) is conserved across many species and expressed at high abundance levels in several tissues
including the kidney, which suggests MALAT1 might be important physiologically. However, MALAT1’s
physiological and pathophysiological role remains largely unknown.
 We discovered recently that renal miR-214-3p targets and suppresses endothelial nitric oxide synthase
(eNOS) directly, which contributes significantly to the development of salt-sensitive hypertension in rat models
and possibly humans. This was supported by a systematic analysis of human sequence variants and all miRNA
precursors, small RNA deep sequencing in human kidney biopsy specimens, kidney-specific inhibition of miR-
214-3p in Dahl SS rats, and a newly generated mutant rat strain. The Dahl SS rat is the model most widely used
to study the molecular mechanism of human salt-sensitive hypertension.
 We have obtained a large series of preliminary data that suggest MALAT1 might be dysregulated in the
kidneys of salt-sensitive humans and SS rats and might influence the development of salt-sensitive hypertension
by regulating the renal miR-214-3p/eNOS pathway. We propose to investigate MALAT1’s role in the
development of salt-sensitive hypertension (Aim 1), the role for the renal miR-214-3p/eNOS pathway in the effect
of MALAT1 on hypertension (Aim 2), and the underlying molecular interactions (Aim 3). We will achieve these
aims by using analysis of scarcely available human samples, combinatorial gene manipulation in animal models,
and new methods including genome editing and RafTOP (rapid freezing with tagged oligonucleotide pullout).
RafTOP is a method for identifying the native interactome for a specific RNA that we developed recently.

## Key facts

- **NIH application ID:** 10338156
- **Project number:** 5R01HL121233-07
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** MINGYU LIANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $385,000
- **Award type:** 5
- **Project period:** 2014-07-17 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10338156

## Citation

> US National Institutes of Health, RePORTER application 10338156, Regulatory RNA in Hypertension (5R01HL121233-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10338156. Licensed CC0.

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