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Updated: Dec 23, 2025
Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
Activated CD4+ T cells-derived exosomal miR-142-3p boosts post-ischemic ventricular remodeling by activating
Lidong Cai1, Gong Chao1, Weifeng Li1
1Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Hongkou District, Shanghai 201620, China.
Insights
Activated CD4+ T cell exosomes promote cardiac fibrosis post-heart attack by delivering miR-142-3p. This microRNA activates WNT signaling, leading to myofibroblast activation and worsening heart dysfunction.
Area of Science:
- Cardiovascular Biology
- Immunology
- Cell Biology
Background:
- Cardiac fibrosis is a key factor in heart dysfunction and failure following myocardial infarction.
- Activated CD4+ T cells contribute to cardiac remodeling, but the precise mechanisms are unclear.
Purpose of the Study:
- To elucidate the role of exosomes from activated CD4+ T cells in cardiac fibrosis.
- To identify the molecular mechanisms by which these exosomes influence cardiac fibroblasts and post-infarction cardiac remodeling.
Main Methods:
- Isolation and characterization of exosomes from activated CD4+ T cells (CD4-activated Exos).
- In vitro studies on cardiac fibroblasts treated with CD4-activated Exos.
- In vivo studies involving delivery of CD4-activated Exos into the heart post-infarction.
- Mechanistic studies involving miR-142-3p, Adenomatous Polyposis Coli (APC), and WNT signaling pathway analysis.
Main Results:
- CD4-activated Exos induced pro-fibrotic effects in cardiac fibroblasts and aggravated cardiac fibrosis and dysfunction post-infarction.
- miR-142-3p, enriched in CD4-activated Exos, mediated these pro-fibrotic effects.
- miR-142-3p directly targeted and inhibited APC, a WNT pathway regulator, leading to WNT pathway activation and cardiac fibroblast activation.
- The study identified an exosomal miR-142-3p-WNT signaling cascade driving myofibroblast activation.
Conclusions:
- CD4-activated exosomes promote post-ischemic cardiac fibrosis via exosomal miR-142-3p-mediated activation of the WNT signaling pathway.
- Targeting exosomal miR-142-3p presents a potential therapeutic strategy for treating cardiac remodeling after myocardial infarction.
Abstract:
Cardiac fibrosis is a primary phenotype of cardiac remodeling that contributes to cardiac dysfunction and heart failure. The expansion and activation of CD4+ T cells in the heart has been identified to facilitate pathological cardiac remodeling and dysfunction; however, the underlying mechanisms remained not well clarified. Herein, we found that exosomes derived from activated CD4+ T cells (CD4-activated Exos) evoked pro-fibrotic effects of cardiac fibroblasts, and their delivery into the heart aggravated cardiac fibrosis and dysfunction post-infarction. Mechanistically, miR-142-3p that was enriched in CD4-activated Exos recapitulated the pro-fibrotic effects of CD4-activated Exos in cardiac fibroblasts, and vice versa. Furthermore, miR-142-3p directly targeted and inhibited the expression of Adenomatous Polyposis Coli (APC), a negative WNT signaling pathway regulator, contributing to the activation of WNT signaling pathway and cardiac fibroblast activation. Thus, CD4-activated Exos promote post-ischemic cardiac fibrosis through exosomal miR-142-3p-WNT signaling cascade-mediated activation of myofibroblasts. Targeting miR-142-3p in CD4-activated Exos may hold promise for treating cardiac remodeling post-MI.
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