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Endothelial Snail Regulates Capillary Branching Morphogenesis via Vascular Endothelial Growth Factor Receptor 3 Expression


Endothelial cells have the intrinsic capacity to shuffle between tip, stalk, and phalanx cells in angiogenic processes. These transitions require the induction or repression of transcripts that are specific for their phenotypes, along with morphological changes. To gain insight into spatiotemporal induction during vascular branching morphogenesis, we used Affymetrix oligonucleotide arrays to screen for Snail. Then, we used stable, small-interfering RNA or the lentivirus-short hairpin RNA system to examine the angiogenic roles of endothelial Snail during retinal capillary morphogenesis. Knockdown of Snail in the developing retinal vasculature impaired deep capillary formation and attenuated vascular endothelial growth factor receptor 3 expression, indicating a functional link between Snail and vascular endothelial growth factor receptor 3. Moreover, we showed vascular endothelial growth factor receptor 3 as a transcriptional target of Snail in vitro. In the retinal vasculature, the deep capillary plexus is a unique vessel with only capillary. The deep capillary plays a critical role in retinal development, neuronal survival, and pathological conditions, including ischemic diseases. Our findings provide molecular insights into the role of the Snail-vascular endothelial growth factor receptor 3 axis in capillary formation under pathophysiological conditions.


Vyšlo v časopise: Endothelial Snail Regulates Capillary Branching Morphogenesis via Vascular Endothelial Growth Factor Receptor 3 Expression. PLoS Genet 11(7): e32767. doi:10.1371/journal.pgen.1005324
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005324

Souhrn

Endothelial cells have the intrinsic capacity to shuffle between tip, stalk, and phalanx cells in angiogenic processes. These transitions require the induction or repression of transcripts that are specific for their phenotypes, along with morphological changes. To gain insight into spatiotemporal induction during vascular branching morphogenesis, we used Affymetrix oligonucleotide arrays to screen for Snail. Then, we used stable, small-interfering RNA or the lentivirus-short hairpin RNA system to examine the angiogenic roles of endothelial Snail during retinal capillary morphogenesis. Knockdown of Snail in the developing retinal vasculature impaired deep capillary formation and attenuated vascular endothelial growth factor receptor 3 expression, indicating a functional link between Snail and vascular endothelial growth factor receptor 3. Moreover, we showed vascular endothelial growth factor receptor 3 as a transcriptional target of Snail in vitro. In the retinal vasculature, the deep capillary plexus is a unique vessel with only capillary. The deep capillary plays a critical role in retinal development, neuronal survival, and pathological conditions, including ischemic diseases. Our findings provide molecular insights into the role of the Snail-vascular endothelial growth factor receptor 3 axis in capillary formation under pathophysiological conditions.


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