Open Access

Overexpression of adrenomedullin protects mesenchymal stem cells against hypoxia and serum deprivation‑induced apoptosis via the Akt/GSK3β and Bcl‑2 signaling pathways

  • Authors:
    • Hongjin Si
    • Yao Zhang
    • Yuqing Song
    • Lili Li
  • View Affiliations

  • Published online on: March 5, 2018     https://doi.org/10.3892/ijmm.2018.3533
  • Pages: 3342-3352
  • Copyright: © Si et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The poor survival rate of transplanted mesenchymal stem cells (MSCs) within the ischemic heart limits their therapeutic potential for cardiac repair. Adrenomedullin (ADM) has been identified as a potent apoptotic inhibitor. The present study aimed to investigate the protective effects of ADM on MSCs against hypoxia and serum deprivation (H/SD)‑induced apoptosis, and to determine the potential underlying mechanisms. In the present study, a recombinant adenovirus expressing the ADM gene was established and was infected into MSCs. The infection rate was determined via microscopic detection of green fluorescence and flow cytometric analysis. The mRNA expression levels of ADM were detected by reverse transcription‑polymerase chain reaction. In addition, a model of H/SD was generated. The MSCs were randomly separated into six groups: Control, enhanced green fluorescent protein (EGFP)‑Adv, EGFP‑ADM, H/SD, EGFP‑Adv + H/SD and EGFP‑ADM + H/SD. Cell viability and proliferation were determined using the Cell Counting kit‑8 assay. Apoptosis was assessed by terminal deoxynucleotidyl transferase‑mediated‑dUTP nick‑end labeling assay and flow cytometric analysis using Annexin V‑phycoerythrin/7‑aminoactinomycin D staining. The protein expression levels of total protein kinase B (Akt), phosphorylated (p)‑Akt, total glycogen synthase kinase (GSK)3β, p‑GSK3β, B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), caspase‑3 and cleaved caspase‑3 were detected by western blot analysis. The results indicated that ADM overexpression could improve MSC proliferation and viability, and protect MSCs against H/SD‑induced apoptosis. In addition, ADM overexpression increased Akt and GSK3β phosphorylation, and Bcl‑2/Bax ratio, and decreased the activation of caspase‑3. These results suggested that ADM protects MSCs against H/SD‑induced apoptosis, which may be mediated via the Akt/GSK3β and Bcl‑2 signaling pathways.
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June-2018
Volume 41 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Si H, Zhang Y, Song Y and Li L: Overexpression of adrenomedullin protects mesenchymal stem cells against hypoxia and serum deprivation‑induced apoptosis via the Akt/GSK3β and Bcl‑2 signaling pathways. Int J Mol Med 41: 3342-3352, 2018
APA
Si, H., Zhang, Y., Song, Y., & Li, L. (2018). Overexpression of adrenomedullin protects mesenchymal stem cells against hypoxia and serum deprivation‑induced apoptosis via the Akt/GSK3β and Bcl‑2 signaling pathways. International Journal of Molecular Medicine, 41, 3342-3352. https://doi.org/10.3892/ijmm.2018.3533
MLA
Si, H., Zhang, Y., Song, Y., Li, L."Overexpression of adrenomedullin protects mesenchymal stem cells against hypoxia and serum deprivation‑induced apoptosis via the Akt/GSK3β and Bcl‑2 signaling pathways". International Journal of Molecular Medicine 41.6 (2018): 3342-3352.
Chicago
Si, H., Zhang, Y., Song, Y., Li, L."Overexpression of adrenomedullin protects mesenchymal stem cells against hypoxia and serum deprivation‑induced apoptosis via the Akt/GSK3β and Bcl‑2 signaling pathways". International Journal of Molecular Medicine 41, no. 6 (2018): 3342-3352. https://doi.org/10.3892/ijmm.2018.3533