Open Access

Exendin-4 enhances the migration of adipose-derived stem cells to neonatal rat ventricular cardiomyocyte-derived conditioned medium via the phosphoinositide 3-kinase/Akt-stromal cell-derived factor-1α/CXC chemokine receptor 4 pathway

  • Authors:
    • Hao Zhou
    • Junjie Yang
    • Ting Xin
    • Tao Zhang
    • Shunyin Hu
    • Shanshan Zhou
    • Guanghui Chen
    • Yundai Chen
  • View Affiliations

  • Published online on: January 22, 2015     https://doi.org/10.3892/mmr.2015.3243
  • Pages: 4063-4072
  • Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Adipose‑derived stem cells (ADSCs) are considered a suitable source of cells for the repair of tissue following acute myocardial infarction (AMI); however, the transplantation efficiency of ADSCs remains low. Therefore, identification of an efficient method to enhance the migration of engrafted cells to the target site is required. The present study used exendin‑4 (Ex‑4), a glucagon‑like peptide‑1 receptor agonist, to optimize the migratory capacity of ADSCs. The aim was to determine the effect and mechanisms of Ex‑4 on the migration of ADSCs to neonatal rat ventricular cardiomyocyte‑derived conditioned medium (NRVC‑CM). The ADSCs and cardiomyocytes were cultured in vitro. Following incubation of the ADSCs with Ex‑4, cell proliferation was measured using an MTT assay and the expression levels of CXC chemokine receptor 4 (CXCR4) were investigated by reverse transctiption quantitative polymerase chain reaction (RT‑qPCR), western blot analysis and flow cytometry. In addition, the expression levels of stromal cell‑derived factor‑1α (SDF‑1α) were evaluated in the NRVC‑CM treated with Ex‑4 by ELISA, RT‑qPCR and western blot analysis. The migration of the ADSCs to the NRVC‑CM was examined using a Transwell assay. Changes in the protein expression levels of phosphorylated (p‑)Akt were examined in the two types of cell by western blot analysis. The results suggested that Ex‑4 promoted the proliferation and expression of CXCR4 in the ADSCs, increased the secretion of SDF‑1α in the cardiomyocytes and increased the expression levels of p‑Akt in both cells. However, the alterations to the SDF‑1α/CXCR4 cascade in the cells were abrogated following pretreatment with LY‑294002, a phosphoinositide 3‑kinase(PI3K) inhibitor. Furthermore, a Transwell migration assay revealed marked translocation of the ADSCs through the membranes, towards the NRVC‑CM, following treatment with Ex‑4. However, these effects were reduced significantly by pretreatment of the cells with the SDF‑1α/CXCR4 cascade antagonist, AMD3100, and the PI3K inhibitor, LY‑294002. These results indicated that Ex‑4 augmented the SDF‑1α/CXCR4 cascade by activating the PI3K/Akt pathways in the ADSCs and NRVCs. Furthermore, enhancement of the PI3K/Akt-SDF-1α/CXCR4 pathway may be important in the migratory response of ADSCs to NRVC‑CM in vitro.
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June-2015
Volume 11 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Zhou H, Yang J, Xin T, Zhang T, Hu S, Zhou S, Chen G and Chen Y: Exendin-4 enhances the migration of adipose-derived stem cells to neonatal rat ventricular cardiomyocyte-derived conditioned medium via the phosphoinositide 3-kinase/Akt-stromal cell-derived factor-1α/CXC chemokine receptor 4 pathway. Mol Med Rep 11: 4063-4072, 2015.
APA
Zhou, H., Yang, J., Xin, T., Zhang, T., Hu, S., Zhou, S. ... Chen, Y. (2015). Exendin-4 enhances the migration of adipose-derived stem cells to neonatal rat ventricular cardiomyocyte-derived conditioned medium via the phosphoinositide 3-kinase/Akt-stromal cell-derived factor-1α/CXC chemokine receptor 4 pathway. Molecular Medicine Reports, 11, 4063-4072. https://doi.org/10.3892/mmr.2015.3243
MLA
Zhou, H., Yang, J., Xin, T., Zhang, T., Hu, S., Zhou, S., Chen, G., Chen, Y."Exendin-4 enhances the migration of adipose-derived stem cells to neonatal rat ventricular cardiomyocyte-derived conditioned medium via the phosphoinositide 3-kinase/Akt-stromal cell-derived factor-1α/CXC chemokine receptor 4 pathway". Molecular Medicine Reports 11.6 (2015): 4063-4072.
Chicago
Zhou, H., Yang, J., Xin, T., Zhang, T., Hu, S., Zhou, S., Chen, G., Chen, Y."Exendin-4 enhances the migration of adipose-derived stem cells to neonatal rat ventricular cardiomyocyte-derived conditioned medium via the phosphoinositide 3-kinase/Akt-stromal cell-derived factor-1α/CXC chemokine receptor 4 pathway". Molecular Medicine Reports 11, no. 6 (2015): 4063-4072. https://doi.org/10.3892/mmr.2015.3243