Original Article

Medical & Biological Engineering & Computing

, Volume 47, Issue 1, pp 41-48

Neuregulin-1 enhances differentiation of cardiomyocytes from embryonic stem cells

  • Zhi WangAffiliated withDepartment of Cardiology, The First People’s Hospital, Shanghai Jiaotong University School of Medicine
  • , Guotong XuAffiliated withKey Laboratory of Stem Cell Biology, Institute of Health Sciences and Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Science, Chinese Academy of Science
  • , Yalan WuAffiliated withKey Laboratory of Stem Cell Biology, Institute of Health Sciences and Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Science, Chinese Academy of Science
  • , Yuan GuanAffiliated withKey Laboratory of Stem Cell Biology, Institute of Health Sciences and Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Science, Chinese Academy of Science
  • , Lu CuiAffiliated withKey Laboratory of Stem Cell Biology, Institute of Health Sciences and Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Science, Chinese Academy of Science
  • , Xia LeiAffiliated withKey Laboratory of Stem Cell Biology, Institute of Health Sciences and Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Science, Chinese Academy of Science
  • , Jingfa ZhangAffiliated withKey Laboratory of Stem Cell Biology, Institute of Health Sciences and Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Science, Chinese Academy of Science
  • , Lisha MouAffiliated withKey Laboratory of Stem Cell Biology, Institute of Health Sciences and Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Science, Chinese Academy of Science
  • , Baogui SunAffiliated withDepartment of Cardiology, The First People’s Hospital, Shanghai Jiaotong University School of Medicine
    • , Qiuyan DaiAffiliated withDepartment of Cardiology, The First People’s Hospital, Shanghai Jiaotong University School of Medicine Email author 

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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