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The role of nuclear factor of activated T cells during phorbol myristate acetate-induced cardiac differentiation of mesenchymal stem cells

Authors
 Hyang-Hee Seo  ;  Chang Youn Lee  ;  Jiyun Lee  ;  Soyeon Lim  ;  Eunhyun Choi  ;  Jong-Chul Park  ;  Seahyoung Lee  ;  Ki-Chul Hwang 
Citation
 STEM CELL RESEARCH & THERAPY, Vol.7(1) : 90, 2016 
Journal Title
 STEM CELL RESEARCH & THERAPY 
Issue Date
2016
MeSH
Cell Cycle/drug effects ; Cell Differentiation/drug effects ; Cyclin-Dependent Kinase Inhibitor p27/genetics ; Cyclin-Dependent Kinase Inhibitor p27/metabolism ; Gene Expression Regulation ; Genes, Reporter ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; Humans ; Lymphocyte Activation/drug effects ; Mesenchymal Stromal Cells/cytology ; Mesenchymal Stromal Cells/drug effects* ; Mesenchymal Stromal Cells/metabolism ; MyoD Protein/genetics ; MyoD Protein/metabolism ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/drug effects* ; Myocytes, Cardiac/metabolism ; Myosin Heavy Chains/genetics ; Myosin Heavy Chains/metabolism ; NFATC Transcription Factors/genetics* ; NFATC Transcription Factors/secretion ; Primary Cell Culture ; Protein Kinase C/genetics ; Protein Kinase C/metabolism ; Signal Transduction ; T-Lymphocytes/cytology ; T-Lymphocytes/drug effects* ; T-Lymphocytes/secretion ; Tetradecanoylphorbol Acetate/pharmacology* ; Transcription, Genetic ; Troponin T/genetics ; Troponin T/metabolism
Keywords
Cardiac differentiation ; MSC ; NFAT ; Phorbol myristate acetate ; Small molecule
Abstract
BACKGROUND: We previously reported that phorbol 12-myristate 13-acetate (PMA) treatment can induce the cardiac differentiation of mesenchymal stem cells (MSCs). In the present study, we investigated how PMA induces cardiac differentiation of MSCs, focusing on its effect on the transcription factors responsible for increased cardiac marker gene expression. METHODS: Human MSCs (hMSCs) were treated with 1 μM PMA for 9 days. The expression of MSC markers and cardiac markers in the PMA-treated hMSC, as well as the nuclear translocation of transcription factors, nuclear factor of activated T cells (NFAT), and myogenic differentiation 1 (MyoD), was examined. Transcriptional activity of NFAT was examined by utilizing a green fluorescent protein (GFP) vector containing NFAT motif of human interleukin-2 promoter. The effect of PMA on the expression of key cell cycle regulators was examined. RESULTS: PMA induces the transcriptional activity of NFAT and MyoD, which have been associated with increased expression of cardiac troponin T (cTnT) and myosin heavy chain (MHC), respectively. Our data suggested that protein kinase C (PKC) mediates the effect of PMA on NFAT activation. Furthermore, PMA treatment increased cell-cycle regulator p27(kip1) expression, suggesting that PMA triggers the cardiac differentiation program in MSCs by regulating key transcription factors and cell cycle regulators. CONCLUSIONS: The results of this study demonstrate the importance of NFAT activation during PMA-induced MSC differentiation and help us to better understand the underlying mechanisms of small molecule-mediated MSC differentiation so that we can develop a strategy for synthesizing novel and improved differentiation-inducing small molecules.
DOI
10.1186/s13287-016-0348-6
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Medical Engineering (의학공학교실) > 1. Journal Papers
Yonsei Authors
Park, Jong Chul(박종철) ORCID logo https://orcid.org/0000-0003-0083-5991
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/151765
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