Related Experiment Video

Updated: Aug 5, 2026

Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
09:16

Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes

Published on: June 3, 2018

Cellular Retinoic Acid-Binding Protein 2 Promotes Ischemia-Induced Cardiac Fibroblast Activation and Fibrosis Through

Zhenyang Su1, Hui Shen1, Jinyu Sun1

  • 1Department of Cardiology The First Affiliated Hospital with Nanjing Medical University Nanjing China.

Journal of the American Heart Association
|July 31, 2026
PubMed
Abstract

Insights

Cellular retinoic acid-binding protein 2 (CRABP2) drives cardiac fibrosis by impairing DNA repair in heart failure. Targeting the CRABP2-MRE11-MRN pathway may limit profibrotic remodeling.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Genetics

Background:

  • Cardiac fibrosis, a key feature of ischemic heart failure, stems from activated myofibroblasts.
  • While DNA damage and repair defects contribute to fibroblast activation, upstream regulators remain unidentified.

Purpose of the Study:

  • To investigate the role of cellular retinoic acid-binding protein 2 (CRABP2) in cardiac fibroblast activation and profibrotic remodeling.
  • To elucidate the molecular mechanisms by which CRABP2 influences DNA damage response and cardiac fibrosis.

Main Methods:

  • Single-cell RNA sequencing of human ischemic cardiomyopathy samples to identify fibroblast-enriched genes.
  • In vivo studies using adeno-associated viruses to modulate CRABP2 in a mouse model of cardiac dysfunction.
  • In vitro experiments with neonatal cardiac fibroblasts to assess CRABP2 function under transforming growth factor-beta (TGF-β) stimulation.
  • Mechanistic investigations including RNA sequencing, immunoprecipitation-mass spectrometry, and DNA damage assays.

Main Results:

  • CRABP2 was identified as a fibroblast-enriched gene upregulated in profibrotic subsets within human ischemic hearts.
  • CRABP2 knockdown preserved cardiac function and reduced fibrosis in mice, while overexpression exacerbated these conditions.
  • In vitro, CRABP2 enhanced TGF-β-induced fibroblast migration, proliferation, activation, and collagen production.
  • CRABP2 was found to bind MRE11, suppress MRN-ATM-CHK2 signaling, and increase DNA damage accumulation.

Conclusions:

  • CRABP2 promotes profibrotic cardiac fibroblast activation by inhibiting MRE11/MRN-mediated DNA repair.
  • The CRABP2-MRE11-MRN axis presents a potential therapeutic target for mitigating fibrotic remodeling in ischemic heart failure.
Keywords:
CRABP2DNA repairMRE11/MRN complexcardiac fibroblastsischemic heart failure

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