# Cardiac Fibroblasts in Postnatal Development and Adult Injury Response

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2024 · $778,115

## Abstract

Abstract
The cardiac fibroblast and its ability to convert into a myofibroblast for extracellular matrix (ECM) production,
ventricular remodeling and the fibrotic response has been an area of recent investigation with important medical
relevance. Here, a dual-PI renewal resubmission application is proposed by a developmental cardiac biologist
and adult disease-based cardiac biologist to address how the postnatal heart matures in adulthood and then
transitions back to a fetal-like program with disease stimulation through direct paracrine crosstalk and ECM
feedback. During the past funding cycle of this award, we identified key regulatory relationships that exist
between myocytes and fibroblasts in both the developing and diseased adult heart, whereby the ECM and
transforming growth factor-β (TGFβ) served as an integrating platform between these 2 cell-types. We have
also observed that fibroblast-expressed GDF10 and the epidermal growth factor (EGF) family member
pleiotrophin (Ptn) mediate critical crosstalk between fibroblasts and myocytes. Here, we will investigate the
hypothesis that TGFβ is a myocyte selective maturation factor that controls fibroblast activity in generating an
effective ECM within the postnatal heart that also underlies adult disease, and that parallel Ptn and GDF10
signaling crosstalk further regulates fibroblast proliferation and promotes cardiomyocyte hypertrophy in
development and disease. The dual-PI renewal application has 3 specific aims: 1) To examine how
cardiomyocyte generated TGFβ1/2/3 and its subsequent signaling to cardiac fibroblasts underlie ECM neonatal
maturation and adult ventricular remodeling, 2) To examine how cardiac fibroblast generated ECM regulates
developmental cardiomyocyte maturation and adult heart remodeling, in part through TGFβ1/2/3
sequestration/release, and 3) To examine the function of the cardiac fibroblast-secreted growth factors Ptn and
GDF10 in postnatal heart development and adult injury. Collectively, these specific aims will uncover novel
signaling mechanisms that underlie heart maturation just after birth and determine how these mechanisms are
redeployed in disease. Thus, the impact of this program will be the identification of novel signaling mechanisms
and effectors that can be therapeutically targeted in human heart disease to positively effect cardiac remodeling
and longstanding fibrosis, with added implications for treating congenital malformations and developmental
growth abnormalities.

## Key facts

- **NIH application ID:** 10809704
- **Project number:** 5R01HL142217-06
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Jeffery D Molkentin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $778,115
- **Award type:** 5
- **Project period:** 2018-07-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10809704

## Citation

> US National Institutes of Health, RePORTER application 10809704, Cardiac Fibroblasts in Postnatal Development and Adult Injury Response (5R01HL142217-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10809704. Licensed CC0.

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