Related Experiment Video

Updated: Feb 2, 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

7.7K

Doxorubicin-induced cardiotoxicity involves IFNγ-mediated metabolic reprogramming in cardiomyocytes

Chen Ni1, Pan Ma2, Ruirui Wang1

  • 1Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, PR China.

The Journal of Pathology
|November 15, 2018
PubMed

Insights

Interferon-gamma (IFNγ) worsens chemotherapy-induced heart damage by disrupting cardiac metabolism. Targeting IFNγ signaling or related metabolic pathways may protect the heart during doxorubicin (DOX) treatment.

Area of Science:

  • Cardiovascular Research
  • Immunology
  • Molecular Biology

Background:

  • Immune responses are implicated in heart disease development.
  • The specific role of interferon-gamma (IFNγ) in doxorubicin (DOX)-induced cardiomyopathy remains unclear.

Purpose of the Study:

  • To investigate the involvement of IFNγ signaling in DOX-induced cardiotoxicity.
  • To elucidate the mechanisms by which IFNγ affects cardiac function during DOX treatment.

Main Methods:

  • Studies were conducted in mice and in vitro using cardiomyocytes.
  • IFNγ receptor expression, downstream signaling, mitochondrial respiration, and fatty acid oxidation were assessed.
  • The AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) axis and p38 signaling were analyzed.

Main Results:

  • DOX treatment activated IFNγ signaling in mouse heart tissue, with high IFNγ receptor expression on cardiomyocytes.
  • In vitro, IFNγ exacerbated DOX-induced cardiomyocyte injury by disrupting mitochondrial respiration and fatty acid oxidation, without affecting cell death.
  • IFNγ extended DOX-induced suppression of the AMPK/ACC axis via a p38-dependent pathway.

Conclusions:

  • IFNγ reprogramming of cardiac metabolism is a key mechanism in DOX-induced cardiomyopathy.
  • Modulating IFNγ signaling or related metabolic pathways (AMPK activation, p38 inhibition) can mitigate DOX cardiotoxicity.
  • This highlights the balance between anti-cancer immunosurveillance and chemotherapy side effects.

Keywords:
IFNγcardiotoxicitydoxorubicinfatty acid metabolism

More Related Videos

Assessing Cardiomyocyte Subtypes Following Transcription Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts09:29

Assessing Cardiomyocyte Subtypes Following Transcription Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts

Published on: March 22, 2017

7.9K
High-Throughput Cardiotoxicity Screening Using Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Monolayers14:03

High-Throughput Cardiotoxicity Screening Using Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Monolayers

Published on: March 24, 2023

2.5K

Related Concept Videos

What is Metabolism?00:52

What is Metabolism?

Overview
131.8K
Receptor-mediated Endocytosis01:39

Receptor-mediated Endocytosis

Overview
110.9K
Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and...
1.5K
Introduction to Nuclear Reprogramming01:14

Introduction to Nuclear Reprogramming

Nuclear reprogramming is the process of switching gene expression of one cell type to that of another cell type, usually from a differentiated cell state to an undifferentiated cell state. Differentiation occurs during processes such as development and morphogenesis, tissue regeneration, and malignancy. Cells can also be artificially induced to reprogram their gene expression by techniques such as nuclear transfer, induced pluripotency, and cell fusion. Such techniques have many applications in...
2.3K
Methods of Nuclear Reprogramming01:24

Methods of Nuclear Reprogramming

Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
2.1K
Induced Pluripotent Stem Cells01:13

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
28.0K