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Neuregulin-1 enhances differentiation of cardiomyocytes from embryonic stem cells

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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.

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Acknowledgments

We thank Chunchun Zhuge, Jianfeng Shen, Hua Jiang, Chunliang Li, Yijun Shi and Lingjie Li for their valuable help in experiments. This work was supported by the Shanghai Science and Technology Committee Grant (No. 030121).

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Authors and Affiliations

  1. Department of Cardiology, The First People’s Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, 200080, Shanghai, China

    Zhi Wang, Baogui Sun & Qiuyan Dai

  2. Key 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, Shanghai, China

    Guotong Xu, Yalan Wu, Yuan Guan, Lu Cui, Xia Lei, Jingfa Zhang & Lisha Mou

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  1. Zhi Wang
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Correspondence to Qiuyan Dai.

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Qiuyan Dai and Baogui Sun are co-corresponding authors contributed equally to this study.

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Wang, Z., Xu, G., Wu, Y. et al. Neuregulin-1 enhances differentiation of cardiomyocytes from embryonic stem cells. Med Biol Eng Comput 47, 41–48 (2009). https://doi.org/10.1007/s11517-008-0383-2

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