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Thymosin β4 impeded murine stem cell proliferation with an intact cardiovascular differentiation

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Summary

Thymosin β4 (Tβ4) is a key factor in cardiac development, growth, disease, epicardial integrity, blood vessel formation and has cardio-protective properties. However, its role in murine embryonic stem cells (mESCs) proliferation and cardiovascular differentiation remains unclear. Thus we aimed to elucidate the influence of Tβ4 on mESCs. Target genes during mESCs proliferation and differentiation were detected by real-time PCR or Western blotting, and patch clamp was applied to characterize the mESCs-derived cardiomyocytes. It was found that Tβ4 decreased mESCs proliferation in a partial dose-dependent manner and the expression of cell cycle regulatory genes c-myc, c-fos and c-jun. However, mESCs self-renewal markers Oct4 and Nanog were elevated, indicating the maintenance of self-renewal ability in these mESCs. Phosphorylation of STAT3 and Akt was inhibited by Tβ4 while the expression of RAS and phosphorylation of ERK were enhanced. No significant difference was found in BMP2/BMP4 or their downstream protein smad. Wnt3 and Wnt11 were remarkably decreased by Tβ4 with upregulation of Tcf3 and constant β-catenin. Under mESCs differentiation, Tβ4 treatment did not change the expression of cardiovascular cell markers α-MHC, PECAM, and α-SMA. Neither the electrophysiological properties of mESCs-derived cardiomyocytes nor the hormonal regulation by Iso/Cch was affected by Tβ4. In conclusion, Tβ4 suppressed mESCs proliferation by affecting the activity of STAT3, Akt, ERK and Wnt pathways. However, Tβ4 did not influence the in vitro cardiovascular differentiation.

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Author information

Authors and Affiliations

  1. Department of Physiology, Chinese-German Stem Cell Center, the Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Hubei Province, Huazhong University of Science and Technology, Wuhan, 430030, China

    Li Nie  (聂 丽), Shi-jun Gao  (高仕君), Ya-nan Zhao  (赵亚楠), Jacob Masika, Hong-yan Luo  (骆红艳), Xin-wu Hu  (胡新武), Liang-pin Zhang  (张亮品) & Hua-min Liang  (梁华敏)

  2. Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, 430030, China

    Li Nie  (聂 丽), Shi-jun Gao  (高仕君), Ya-nan Zhao  (赵亚楠), Jacob Masika, Hong-yan Luo  (骆红艳), Xin-wu Hu  (胡新武), Liang-pin Zhang  (张亮品) & Hua-min Liang  (梁华敏)

  3. College of Pharmacy, Wuhan Institute of Bioengineering, Wuhan, 430415, China

    Li Nie  (聂 丽)

  4. Department of Medical Physiology, Faculty of Health Sciences, Egerton University, Nakura, 53620115, Kenya

    Jacob Masika

  5. Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China

    Ying Zeng  (曾 莹)

  6. Institute of Neurophysiology, University of Cologne, Robert Koch str. 39, Cologne, 50931, Germany

    Jürgen Hescheler

  7. School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China

    Li Nie  (聂 丽), Shi-jun Gao  (高仕君), Ya-nan Zhao  (赵亚楠), Jacob Masika, Hong-yan Luo  (骆红艳), Xin-wu Hu  (胡新武), Liang-pin Zhang  (张亮品) & Hua-min Liang  (梁华敏)

Authors
  1. Li Nie  (聂 丽)
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  2. Shi-jun Gao  (高仕君)
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  3. Ya-nan Zhao  (赵亚楠)
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  4. Jacob Masika
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  5. Hong-yan Luo  (骆红艳)
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  6. Xin-wu Hu  (胡新武)
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  7. Liang-pin Zhang  (张亮品)
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  8. Ying Zeng  (曾 莹)
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  9. Jürgen Hescheler
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  10. Hua-min Liang  (梁华敏)
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Corresponding author

Correspondence to Hua-min Liang  (梁华敏).

Additional information

This project was supposed by grants from National Natural Science Foundation of China (No. 81100818, No. 31100828 and No. 81070342), and the Fundamental Research Funds for the Central Universities (HUST: No. 2012TS036).

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Nie, L., Gao, Sj., Zhao, Yn. et al. Thymosin β4 impeded murine stem cell proliferation with an intact cardiovascular differentiation. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 36, 328–334 (2016). https://doi.org/10.1007/s11596-016-1587-6

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  • DOI: https://doi.org/10.1007/s11596-016-1587-6

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