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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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          Author and article information

          Journal
          In Vitro Cell Dev Biol Anim
          In vitro cellular & developmental biology. Animal
          Springer Science and Business Media LLC
          1543-706X
          1071-2690
          May 2016
          : 52
          : 5
          Affiliations
          [1 ] Department of Cardiology, Chinese PLA General Hospital, #28 Fuxing Rd, Beijing, 100853, China.
          [2 ] Department of Radiotherapy, Beijing Cancer Hospital, Beijing, China.
          [3 ] Department of Emergency, Jishuitan Hospital, Tianjin, China.
          [4 ] Department of Cardiology, Chinese PLA General Hospital, #28 Fuxing Rd, Beijing, 100853, China. yundaic@163.com.
          Article
          10.1007/s11626-016-0003-7
          10.1007/s11626-016-0003-7
          26932601
          0a0b1ef2-3787-42a0-aad8-ee3ed21081b9
          History

          Adipose-derived stem cells,Exendin-4,JNK/ERK signaling pathway,Proliferation

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