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 microg/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.

• Authors: Xian-bao Liu, Jun Jiang, Chun Gui, Xin-yang Hu, Mei-xiang Xiang, Jian-an Wang
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 29 Issue 7 Pg. 815-22 (Jul 2008) ISSN: 1745-7254 [Electronic] United States
• PMID: 18565279 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiopoietin-1
• Culture Media, Serum-Free
• Phosphatidylinositol 3-Kinases
• Oncogene Protein v-akt
• Caspases

Topics

• Angiopoietin-1 (pharmacology)
• Animals
• Apoptosis (drug effects)
• Caspases (physiology)
• Cell Survival (drug effects)
• Culture Media, Serum-Free
• Humans
• Hypoxia (pathology, prevention & control)
• In Situ Nick-End Labeling
• Mesenchymal Stem Cells (drug effects)
• Muscle, Smooth, Vascular (drug effects)
• Oncogene Protein v-akt (physiology)
• Phosphatidylinositol 3-Kinases (physiology)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)