Cellular and Molecular Pharmacology

Angiopoietin-1 protects mesenchymal stem cells against serum deprivation and hypoxia-induced apoptosis through the PI3K/Akt pathway

Abstract

Aim:

The angiopoietin-1 (Ang1)/Tie-2 signaling system not only plays a pivotal role in vessel growth, remodeling, and maturation, but also reduces apoptosis of endothelial cells, neurons, and cardiomyocytes. However, relatively little is known as to whether Ang1 has a protective effect on mesenchymal stem cells (MSC). The aim of the present study was to investigate the protective effect of Ang1/Tie-2 signaling on MSC against serum deprivation and hypoxia-induced apoptosis, and to determine the possible mechanisms.

Methods:

Hoechst 33342 and terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling staining were used to assess the apoptosis of MSC. The expression of Tie-2, Akt, Bcl-2, Bax, and cleaved caspase-9 and -3 was detected by Western blot analysis.

Results:

This study showed that MSC expressed Tie-2 receptor, and Ang1 induced Tie-2 receptor phosphorylation. The protective effect of Ang1 on MSC was dose-dependent and peaked at 50 μg/L; however, the soluble Tie-2/Fc fusion protein, which acts as an inhibitor by sequestering Ang1, abrogated the anti-apoptotic effect. Ang1 induced Akt phosphorylation, increased the Bcl-2/Bax ratio, and decreased the activation of caspase-9 and -3. All these effects were attenuated by Tie-2/Fc and a phosphatidylinositol 3 kinase (PI3K) inhibitor, wortmannin.

Conclusion:

These results demonstrate that Ang1 can protect MSC against serum deprivation and hypoxia-induced apoptosis; Ang1/Tie-2 signaling and its downstream PI3K/Akt messenger pathway are crucial in the processes leading to MSC survival.

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Correspondence to Jian-an Wang.

Additional information

Project supported by the National Natural Science Foundation of China (No 30670868) and the Natural Science Foundation of Zhejiang Province (No R206007).

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Liu, Xb., Jiang, J., Gui, C. et al. Angiopoietin-1 protects mesenchymal stem cells against serum deprivation and hypoxia-induced apoptosis through the PI3K/Akt pathway. Acta Pharmacol Sin 29, 815–822 (2008). https://doi.org/10.1111/j.1745-7254.2008.00811.x

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Keywords

  • mesenchymal stem cells
  • angiopoietin-1
  • Tie-2 receptor
  • apoptosis

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