Neuregulin-1 enhances differentiation of cardiomyocytes from embryonic stem cells

  • Zhi Wang
  • Guotong Xu
  • Yalan Wu
  • Yuan Guan
  • Lu Cui
  • Xia Lei
  • Jingfa Zhang
  • Lisha Mou
  • Baogui Sun
  • Qiuyan Dai
Original Article

Abstract

Neuregulin-1 (NRG-1) is a multifunctional regulator that acts through receptor tyrosine kinases of the epidermal growth factor (EGF/ErbB) receptor family in diverse tissue. ErbB receptors are expressed in developing embryoid bodies (EBs), and the importance of the NRG-1/ErbB signaling axis in heart development has been investigated, but the underlying molecular mechanism is poorly studied. NRG-1 treatment at 100 ng/ml significantly increased the number of beating EBs of differentiated murine embryonic stem cells (ESCs). Furthermore, NRG-1 up-regulated the expression of the cardiac-restricted transcription factors Nkx2.5 and GATA-4 and factors involved in differentiated cardiac cells (α-MHC, β-MHC and α-actinin); NRG-1-induced increase of Nkx2.5 transcription was inhibited by treatment with the PI3 K inhibitor or ErbB receptor inhibitor. Western blot analysis confirmed that the expression of phospho-Akt in the beating foci was increased in the presence of NRG-1. Our results suggest that NRG-1 promotes cardiomyocyte differentiation of ESCs and the ErbB/PI3 K/Akt signaling pathway is one of the underlying molecular mechanisms.

Keywords

Neuregulin-1 Embryonic stem cells Cardiomyocytes Phosphatidylinositol 3-kinase 

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Copyright information

© International Federation for Medical and Biological Engineering 2008

Authors and Affiliations

  • Zhi Wang
    • 1
  • Guotong Xu
    • 2
  • Yalan Wu
    • 2
  • Yuan Guan
    • 2
  • Lu Cui
    • 2
  • Xia Lei
    • 2
  • Jingfa Zhang
    • 2
  • Lisha Mou
    • 2
  • Baogui Sun
    • 1
  • Qiuyan Dai
    • 1
  1. 1.Department of Cardiology, The First People’s HospitalShanghai Jiaotong University School of MedicineShanghaiChina
  2. 2.Key Laboratory of Stem Cell Biology, Institute of Health Sciences and Institute of Biochemistry and Cell BiologyShanghai Institute for Biological Science, Chinese Academy of ScienceShanghaiChina

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