# ZFP36, an RNA Binding Protein that Regulates DNA Repair and Cell Proliferation in PAH

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $393,750

## Abstract

SUMMARY
Pulmonary Arterial Hypertension (PAH) is a pulmonary vascular disease characterized by increased pulmonary
arterial pressure. PAH patients are young, have poor life quality, and have a short life expectancy. This
daunting fact underscores our need for innovative approaches in PAH. PAH arises from a pro-proliferative and
anti-apoptotic phenotype of pulmonary arterial smooth muscle cells (PASMC), endothelial cells (PAEC), and
fibroblast. Recent advances linked this phenotype to a genome-wide deregulation of gene expression.
Therefore, it is imperative to decode the cause of this deregulation to find new therapies. Regulation of gene
expression is governed, in large part, by one main class of protein: RNA-binding proteins (RBP). RBPs
regulate the fate of hundreds of transcripts at once through the recognition of specific motifs that confer them a
high therapeutic potential. However, limited data exist on their implication in PAH. Here, using large-scale
transcriptomic data from PAH patients' lungs, and cultured PASMC and PAEC, we found ZFP36 an RBP
increased in lungs and further enriched in PASMC but not in PAEC. We used computational biology to identify
the targets of ZFP36 and characterize their functions in PAH-PASMC. Our data show that ZFP36 targets are
lead actors in DNA repair and resistance to apoptosis (e.g. RFC3) and cell cycle (e.g. ANAPC4). In-vitro
experiment on PAH-PASMC confirmed the up-regulation of ZFP36 targets and the role of ZFP36 in their up-
regulation, as well as the role of ZFP36 in DNA repair and cell cycle. In addition, we found that inhibition of
ZFP36 in Sugen/Hypoxia rats reduced PH severity.

## Key facts

- **NIH application ID:** 10937804
- **Project number:** 1R01HL174472-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Mansoureh Eghbali
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $393,750
- **Award type:** 1
- **Project period:** 2024-07-20 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10937804

## Citation

> US National Institutes of Health, RePORTER application 10937804, ZFP36, an RNA Binding Protein that Regulates DNA Repair and Cell Proliferation in PAH (1R01HL174472-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10937804. Licensed CC0.

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