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Akt promotes endocardial-mesenchyme transition
Kafi N Meadows1, Seema Iyer, Mark V Stevens
1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Journal of Angiogenesis Research
|December 1, 2009
Summary
Akt signaling drives endothelial to mesenchymal transition (EndMT) in the developing heart. This study clarifies Akt1
Area of Science:
- Cardiovascular Development
- Cell Biology
- Molecular Signaling
Background:
- Endothelial to mesenchymal transition (EndMT) is crucial for heart development, specifically endocardial cushion formation.
- Separating EndMT commitment from mesenchymal cell proliferation and migration has been challenging.
- The precise molecular triggers for endothelial cell commitment to EndMT remain incompletely understood.
Purpose of the Study:
- To investigate the role of Akt signaling in the initial commitment of endothelial cells to EndMT.
- To elucidate the specific functions of Akt signaling in driving EndMT during heart development.
Main Methods:
- Analysis of Akt1 mRNA expression in developing heart endocardium.
- Inhibition of the PI3K/Akt pathway using LY294002 in atrioventricular canal explant cultures.
- Overexpression of constitutively active Akt1 (myrAkt1) in endothelial cells.
- Utilizing a transgenic model with inducible myrAkt1 expression in endocardial cells.
Main Results:
- Akt1 mRNA was localized to the endocardium during endocardial cushion formation.
- PI3K/Akt pathway inhibition impaired mesenchyme outgrowth in explant cultures.
- Constitutively active Akt1 downregulated endothelial marker VE-cadherin and upregulated mesenchymal markers N-cadherin and Snail.
- Targeted Akt1 signaling in endocardial cells confirmed its role in driving EndMT initiation.
Conclusions:
- Akt signaling plays a central role in committing endothelial cells to the EndMT process.
- Akt1 signaling is a key driver of EndMT in the developing heart endocardium.
- This study distinguishes the role of Akt signaling in EndMT commitment from its functions in mesenchymal cells.
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