# Promoting Cardiomyocyte Cell Cycle Activity and Cardiac Regeneration through IL13 Signaling

> **NIH NIH F31** · MEDICAL COLLEGE OF WISCONSIN · 2020 · $45,520

## Abstract

Title: Promoting Cardiomyocyte Cell Cycle Activity and Cardiac Regeneration through IL13 Signaling
Project Summary
Close to 6 million people in the United States have heart failure (HF), which costs the nation an estimated
$30.7 billion each year. HF occurs when the heart has a reduced ability to pump blood which is usually caused
by diminished contractility of the myocardium. Studying cardiac regeneration in lower vertebrates provides a
unique opportunity to elucidate pro-regenerative mechanisms to restore function in the heart. Interestingly, the
neonatal mouse contains the ability to regenerate myocardium during its first week of life. Previous work
uncovered a role for Interleukin 13 (IL13) in directly stimulating cardiomyocyte cell cycle activity and neonatal
cardiac regeneration in the mouse. IL13 signals through the IL4Ra/IL13Ra1 heterodimer receptor, which is
present on cardiomyocytes through adulthood. Preliminary experiments looking at the knockout of IL4Ra
indicate diminished cell cycle activity and lack of cardiac regeneration when compared to wildtype littermate
controls. Additionally, DNA synthesis and MI recovery were improved in 7-day old, non-regenerative mice
when administered exogenous IL13. Overall, this proposal addresses the hypothesis that IL13 signaling
enhances cardiomyocyte cell cycle activity and promotes cardiac regeneration in neonatal and adult
mice. The following proposed experiments will investigate the cardio-regenerative potential of IL13 signaling
both endogenously and exogenously. Specific Aim 1 will test the hypothesis that IL4Ra/IL13Ra1 depletion on
cardiomyocytes will inhibit cell cycle activity and cardiac regeneration. Both in vitro and in vivo experiments will
assess the endogenous role of IL13 directly on cardiomyocytes. The in vivo experiments will examine
regenerative potential in a novel mouse model (IL4Rafl/fl Myh6CRE) which have a cardiomyocyte-specific
depletion of IL4Ra. Aim 2 will address the hypothesis that exogenous administration of IL13 will promote
cardiac regeneration and cell cycle activity in adult mice. Myocardial infarctions will be induced in 8-10 week
old mice, followed by daily administration of recombinant IL13 for 4 weeks. Upon collection, cardiac function
and proliferative potential will be analyzed through histology, qPCR, BrdU/EdU incorporation, and
echocardiography.

## Key facts

- **NIH application ID:** 9907028
- **Project number:** 1F31HL150919-01
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Samantha J Paddock
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 1
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9907028

## Citation

> US National Institutes of Health, RePORTER application 9907028, Promoting Cardiomyocyte Cell Cycle Activity and Cardiac Regeneration through IL13 Signaling (1F31HL150919-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9907028. Licensed CC0.

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