# Cardiac fibroblasts in postnatal development and adult injury response

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $694,633

## Abstract

Abstract
The cardiac myocyte has long been the primary focus of studies attempting to elucidate the
regulatory aspects underlying cardiac development and disease. However, recently the
involvement of nonmyocytes has emerged as potentially just as important as myocytes in
contributing to and controlling cardiac remodeling during development and progressive
pathogenesis in ischemia-induced heart failure. More specifically, the cardiac fibroblast and its
ability to convert to myofibroblasts in promoting ECM production, ventricular remodeling and the
fibrotic response have been underappreciated as critical regulator of cardiac biology. Here we
propose a dual-PI application led by developmental and adult disease-based cardiac investigators
to address key areas of fibroblast biology that span the early postnatal heart up through the failing
and fibrotic adult heart. Previously, the field had not been able to carefully annotate the functional
aspects of the fibroblast within the developing and diseased heart, in part because of a lack of
appropriate genetic tools that specifically target this cell-type. More recently we and others have
generated a few critical genetically modified mouse models that specifically target resident cardiac
fibroblasts, as well as all activated fibroblasts and myofibroblasts in the heart. Thus, here we can
now test the novel and overarching hypothesis that activated fibroblasts and myofibroblasts play
selective roles in early neonatal ventricular maturation, regeneration and heart development,
which is recapitulated in the adult heart in response acute and chronic ischemia-induced disease
states. The dual-PI application has 3 specific aims: 1) To define sub-stages and functions of
cardiac fibroblasts and myofibroblasts during postnatal development and in the adult heart
following acute and chronic disease stimulation, 2) To identify crosstalk mechanisms between
cardiac fibroblasts and myocytes in the developing and diseased heart, and 3) To define Tcf21-
mediated contributions to fibroblast lineage expansion and commitment in the developing
postnatal heart and in the adult heart after ischemic and acute injury. Collectively, these specific
aims will uncover stages of fibroblast differentiation during development, regeneration and
hypertrophy across both models of interstitial fibrosis and replacement fibrosis. Such an
understanding will lay the foundation for future studies into specific therapeutic pathways to target
in treating longstanding fibrotic heart disease states or to enhance the regenerative capacity of
the heart.

## Key facts

- **NIH application ID:** 9949447
- **Project number:** 5R01HL142217-03
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Jeffery D Molkentin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $694,633
- **Award type:** 5
- **Project period:** 2018-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9949447

## Citation

> US National Institutes of Health, RePORTER application 9949447, Cardiac fibroblasts in postnatal development and adult injury response (5R01HL142217-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9949447. Licensed CC0.

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