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In Vitro Differentiation of Human Mesenchymal Stem Cells into Functional Cardiomyocyte-like Cells
Published on: August 9, 2017
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Exosomes from Suxiao Jiuxin pill-treated cardiac mesenchymal stem cells decrease H3K27 demethylase UTX expression in
Xiao-Fen Ruan1,2, Yong-Jun Li3,2, Cheng-Wei Ju3,2
1Cardiovascular Department, Cardiovascular Research Institute of Traditional Chinese Medicine, Shuguang Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Acta Pharmacologica Sinica
|March 16, 2018
Summary
Suxiao Jiuxin pill (SJP) treatment modifies exosomes from cardiac stem cells to promote cardiomyocyte proliferation. These SJP-modified exosomes induce epigenetic changes, increasing histone 3 lysine 27 trimethylation and suppressing UTX expression, ultimately enhancing cardiac cell replication.
Area of Science:
- Cardiovascular Biology
- Stem Cell Biology
- Epigenetics
Background:
- Suxiao Jiuxin pill (SJP) is a traditional Chinese medicine used for acute coronary syndrome.
- The molecular mechanisms of SJP's cardiac benefits are not fully understood.
- Cardiac mesenchymal stem cell (C-MSC)-derived exosomes play a role in cardiac repair through epigenetic regulation.
Purpose of the Study:
- To investigate if SJP treatment alters C-MSC-derived exosomes to induce epigenetic remodeling in recipient cardiomyocytes.
- To explore the impact of SJP-modified exosomes on cardiomyocyte proliferation and epigenetic markers.
Main Methods:
- Isolated C-MSCs were pretreated with SJP, tetramethylpyrazine (TMP), or borneol (BOR).
- HL-1 cardiomyocytes were treated with exosomes derived from control C-MSCs (Ctrl-Exos) or SJP-pretreated C-MSCs (SJP-Exos).
- Analyzed protein levels of histone 3 lysine 27 trimethylation (H3K27me3) and mRNA expression of histone methylases/demethylases (EZH1, EZH2, EED, JMJD3, UTX).
- Assessed cardiomyocyte proliferation using PCNA as a marker.
Main Results:
- SJP-Exos significantly increased H3K27me3 levels in HL-1 cells, a marker of transcriptional suppression.
- SJP-Exos selectively suppressed UTX expression in recipient cardiomyocytes.
- Proliferating Cell Nuclear Antigen (PCNA) levels, a marker of cell replication, were significantly higher in SJP-Exo-treated cells.
Conclusions:
- SJP treatment modulates C-MSC-derived exosomes to induce epigenetic chromatin remodeling in cardiomyocytes.
- SJP-Exosomes enhance cardiomyocyte proliferation by increasing H3K27me3 and suppressing UTX.
- SJP-derived exosomes show potential for promoting cardiomyocyte proliferation in cardiac repair.
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