Related Experiment Video
Updated: Jun 5, 2025
09:16
Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
7.2K
Transcription Factor 21 Regulates Cardiac Myofibroblast Formation and Fibrosis
Anne Katrine Z Johansen1, Rajesh K Kasam1, Ronald J Vagnozzi1,2
1Division of Molecular Cardiovascular Biology (A.K.Z.J., R.K.K., R.J.V., S.-C.J.L., S.L.K.B., Y.K., K.M.G., K.W., M.A.S., T.A.B., J.D.M.), Department of Pediatrics, University of Cincinnati and Cincinnati Children's Hospital Medical Center, OH.
Circulation Research
|December 4, 2024
Summary
Transcription factor 21 (TCF21) does not maintain adult cardiac fibroblast identity but prevents fibrosis when its downregulation is inhibited. Preventing TCF21 loss reduces myofibroblast formation and cardiac fibrosis after injury.
Area of Science:
- Cardiovascular Biology
- Cellular and Molecular Medicine
- Fibrosis Research
Background:
- TCF21 (transcription factor 21) is a bHLH protein crucial for embryonic cardiac fibroblast (CF) development.
- In adult hearts, TCF21 is downregulated during injury, suggesting a role in regulating fibroblast differentiation and fibrosis.
Purpose of the Study:
- To investigate the role of TCF21 in adult cardiac fibroblast differentiation and cardiac fibrosis.
- To determine the effects of TCF21 gain-of-function and loss-of-function on cardiac injury responses.
Main Methods:
- Utilized tamoxifen-inducible Cre mouse models for TCF21 deletion or enforced expression in adult CFs.
- Performed histological, echocardiographic, and transcriptomic analyses.
- Identified genomic TCF21 occupancy via ChIP-seq.
- Employed myocardial infarction and AngII/phenylephrine models for cardiac fibrosis.
Main Results:
- TCF21 deletion in adult CFs did not affect fibroblast numbers, myofibroblast differentiation, or fibrosis.
- Enforced TCF21 expression inhibited myofibroblast differentiation and reduced cardiac fibrosis and hypertrophy.
- Sustained TCF21 expression prevented the induction of fibrosis-related genes and ECM organization.
Conclusions:
- TCF21 is not essential for maintaining adult CF identity.
- Inhibiting TCF21 downregulation during injury reduces myofibroblast formation, cardiac fibrosis, and acute hypertrophic responses.
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