Open AccessAngiopoietin‐1 protects mesenchymal stem cells against serum deprivation and hypoxia‐induced apoptosis through the PI3K/Akt pathway 1
Author(s) -
LIU Xianbao,
JIANG Jun,
GUI Chun,
HU Xinyang,
XIANG Meixiang,
WANG Jianan
Publication year - 2008
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2008.00811.x
Subject(s) - wortmannin , apoptosis , pi3k/akt/mtor pathway , protein kinase b , microbiology and biotechnology , angiopoietin , mesenchymal stem cell , tunel assay , signal transduction , chemistry , biology , cancer research , vascular endothelial growth factor , biochemistry , vegf receptors
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.