Histone deacetylase inhibitor Trichostatin A promotes cardiomyocyte differentiation of mesenchymal stem cells

  • Jie Tian, Department of Cardiology, Children's Hospital of Chongqing Medical University, China
  • Ge Yang, Department of Cell and Molecular Biology, Pediatric Institute of Chongqing Medical University, China
  • Jing Zhu, Department of Cell and Molecular Biology, Pediatric Institute of Chongqing Medical University, China
  • Yuan Chen, Department of Cardiology, Children’s Hospital of Chongqing Medical University, China
  • Chuan Feng, Department of Cardiology, Children’s Hospital of Chongqing Medical University, China
  • Lili Zhao, Department of Cardiology, Children’s Hospital of Chongqing Medical University, China
  • Tewei Lv, Department of Cardiology, Children’s Hospital of Chongqing Medical University, China

    • Background: This study was designed to investigate the effect of histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) on the differentiation potential of mesenchymal stem cells (MSCs) into cardiomyocytes.
    Methods: Adult rat bone marrow MSCs were co-cultured with rat cardiomyocytes in the presence of 5-azacytidine (5-aza), with or without the treatment of different concentrations of TSA (100nmol/L, 300 nmol/L and 500 nmol/L) for 72 hrs. mRNA expression of early transcription factors related to cardiac muscle cells—GATA-4,NKx2.5,MEF2c was evaluated using real time RT-PCR and the protein expression of cardiac troponin T (cTnT) was determined using immunofluorescence staining and Western blotting .
    Results: One week after the co-culture of MSCs with pulsating cardiac muscle cells, the cardiomyocyte differentiation began to occur in MSCs. A significant amount of cTnT protein were detected in two kinds of induction including the co-culture with rat cardiomyocytes and 5-aza, cTnT protein levels were significantly increased after TSA intervention of 72 hrs as the TSA concentration levels vary, the expression of cTnT was up-regulated in a trend of concentration gradient, and associated with constitutive activation of early transcription factors of cardiac muscle cells—GATA-4,NKx2.5,MEF2c in MSCs. However, GATA-4,NKx2.5,MEF2c mRNA levels were significantly up-regulated after intervened 72 hrs as the concentration levels of TSA vary in two kinds of induction.
    Conclusion: Inhibition of HDAC facilities the ability of MSC differentiation into cardiomyocyte, which manifests an important role of acetylation in the regulation of cell differentiation.