Neuregulin-1 enhances differentiation of cardiomyocytes from embryonic stem cells.
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 (alpha-MHC, beta-MHC and alpha-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.
Wang
Zhi
Z
Department of Cardiology, The First People's Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, 200080 Shanghai, China.
Xu
Guotong
G
Wu
Yalan
Y
Guan
Yuan
Y
Cui
Lu
L
Lei
Xia
X
Zhang
Jingfa
J
Mou
Lisha
L
Sun
Baogui
B
Dai
Qiuyan
Q
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D020890:Neuregulin-1; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects
D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; C490581:Nrg1 protein, mouse