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Exendin-4 promotes proliferation of adipose-derived stem cells through ERK and JNK signaling pathways

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Abstract

Adipose-derived stem cell (ADSC) transplantation has emerged as a potential tool for the treatment of cardiovascular disease. However, with a limited renewal capacity and the need for mass cells during the engraftment, strategies are needed to enhance ADSC proliferative capacity. In this study, we explored the effects of exendin-4 (Ex-4), a glucagon-like peptide-1 analog, on the growth of ADSCs, focusing in particular on c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) signaling pathways. Firstly, ADSCs were isolated and cultured in vitro. Then, flow cytometry demonstrated that ADSCs were positive for CD90 and CD29 but negative for CD31, CD34, and CD45. Ex-4 (0–50 nM) treatment increased ADSC proliferation in a dose-dependent manner but had no effects on stem cell markers of ADSCs. Moreover, we found that Ex-4 treatment elevated the phosphorylation levels of the JNK and ERK signaling pathways. Furthermore, utilization of Ex-4 also promoted cyclin D1 and cyclin E protein expression, which was accompanied by more Edu+ cells and a higher percentage of cells in the S-phase of the cell cycle after Ex-4 treatment. In parallel, the application of inhibitors SP600125 and PD98059, inhibitors of the JNK and ERK signaling pathways, respectively, not only reversed such effects of Ex-4 on JNK and ERK but also resulted in lower percentages of S-phase cells and fewer numbers of Edu+ cells. In summary, Ex-4 has no effects on stem cell markers in ADSCs but promotes ADSC growth via JNK and ERK signaling pathways.

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Acknowledgments

The present study was performed in accordance with the Declaration of Helsinki and the guidelines of the Ethics Committee of the Chinese PLA (People’s Liberty Army) General Hospital, Beijing, China.

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    Authors and Affiliations

    1. Department of Cardiology, Chinese PLA General Hospital, #28 Fuxing Rd, Beijing, 100853, China

      Ying Zhang, Hao Zhou, Shunyin Hu, Ying Zhou, Tianwen Han & Yundai Chen

    2. Department of Radiotherapy, Beijing Cancer Hospital, Beijing, China

      Shi Chen

    3. Department of Emergency, Jishuitan Hospital, Tianjin, China

      Baichuan Liu

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    1. Ying Zhang
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    2. Shi Chen
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    3. Baichuan Liu
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    4. Hao Zhou
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    Correspondence to Yundai Chen.

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    Editor: Tetsuji Okamoto

    Ying Zhang, Shi Chen, Baichuan Liu, Hao Zhou and Shunyin Hu contributed equally to this work.

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    Zhang, Y., Chen, S., Liu, B. et al. Exendin-4 promotes proliferation of adipose-derived stem cells through ERK and JNK signaling pathways. In Vitro Cell.Dev.Biol.-Animal 52, 598–606 (2016). https://doi.org/10.1007/s11626-016-0003-7

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