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Published on: November 18, 2009
Interaction of galectin-1 with caveolae induces mouse embryonic stem cell proliferation through the Src, ERas, Akt
1Department of Veterinary Physiology, Biotherapy Human Resources Center, Chonnam National University, Gwangju, Korea.
Abstract:
Galectins have the potential to provide a promising alternative for unveiling the complexity of embryonic stem (ES) cell self-renewal, although the mechanism by which galectins maintain ES cell self-renewal has yet to be identified. Galectin-1 increased [(3)H]-thymidine incorporation as well as cyclin expression and decreased p27(kip1) expression. Src and caveolin-1 phosphorylation was increased by galectin-1, and phospho-caveolin-1 was inhibited by PP2. In addition, inhibition of caveolin-1 by small interfering RNA and methyl-beta-cyclodextrin (Mbeta-CD) decreased galectin-1-induced cyclin expression and [(3)H]-thymidine incorporation. Galectin-1 caused Akt and mTOR phosphorylation, which is involved in cyclin expression. Galectin-1-induced phospho-Akt and -mTOR was inhibited by PP2, ERas siRNA, caveolin-1 siRNA and Mbeta-CD. Furthermore, mTOR phosphorylation was decreased by LY294002 and Akt inhibitor. Galectin-1-induced increase in cyclin expression and decrease in p27(kip1) was blocked by Akt inhibitor and rapamycin. In conclusion, galectin-1 increased DNA synthesis in mouse ES cells via Src, caveolin-1 Akt, and mTOR signaling pathways.
Insights
Galectin-1 promotes embryonic stem cell self-renewal by increasing DNA synthesis. This process involves key signaling pathways including Src, caveolin-1, Akt, and mTOR.
Area of Science:
- Stem Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Embryonic stem (ES) cell self-renewal is crucial for development and regenerative medicine.
- The precise mechanisms regulating ES cell self-renewal are complex and not fully understood.
- Galectins are implicated in cellular processes, but their role in ES cell self-renewal requires elucidation.
Purpose of the Study:
- To investigate the role of galectin-1 in maintaining mouse embryonic stem cell self-renewal.
- To identify the specific molecular pathways mediating galectin-1's effects on ES cells.
Main Methods:
- Assessed DNA synthesis using [(3)H]-thymidine incorporation.
- Measured expression levels of cyclins and p27(kip1).
- Analyzed protein phosphorylation of Src, caveolin-1, Akt, and mTOR using Western blotting and specific inhibitors (PP2, Mbeta-CD, ERas siRNA, LY294002, Akt inhibitor, rapamycin).
Main Results:
- Galectin-1 significantly increased [(3)H]-thymidine incorporation and cyclin expression while decreasing p27(kip1) expression.
- Galectin-1 induced phosphorylation of Src, caveolin-1, Akt, and mTOR.
- Inhibition of Src, caveolin-1, Akt, or mTOR pathways abrogated galectin-1's effects on DNA synthesis and cyclin expression.
Conclusions:
- Galectin-1 enhances DNA synthesis in mouse ES cells.
- The pro-self-renewal effects of galectin-1 are mediated through the Src, caveolin-1, Akt, and mTOR signaling cascade.
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