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ZEB1 Modifies VE-Cadherin Signaling in Lymphatic Endothelial Cells.

Nada S Ahmed1,2, Joseph L Horder1, Charles T Cresswell1

  • 1Endothelial Quiescence Group, Centre for Cancer Sciences, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham, UK.

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Summary
This summary is machine-generated.

Zinc finger E-box-binding homeobox 1 (ZEB1) maintains lymphatic endothelial barrier integrity. ZEB1 signaling impacts VE-cadherin phosphorylation and YAP1 expression, crucial for lymphatic vessel function.

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Vascular Biology

Background:

  • Zinc finger E-box-binding homeobox 1 (ZEB1) is a transcription factor involved in epithelial-to-mesenchymal transition (EMT) and cell fate.
  • Endothelial ZEB1 signaling influences blood vessel growth and junctional integrity, but its role in lymphatic vasculature is unknown.
  • Regulation of lymphatic integrity by VE-cadherin requires further elucidation.

Purpose of the Study:

  • Identify ZEB1-dependent signaling pathways in lymphatic endothelial cells (LECs).
  • Investigate the role of ZEB1 in lymphatic endothelial barrier function and VE-cadherin regulation.

Main Methods:

  • Integrated proteomic and transcriptomic analysis in lymphatic endothelial cells (LECs).
  • ZEB1 knockdown and YAP1 silencing experiments.
  • Assessment of VE-cadherin phosphorylation, monolayer resistance, impedance, and leukocyte transendothelial migration.

Main Results:

  • Loss of ZEB1 reduced VE-cadherin phosphorylation at pY731 and pY685, decreasing monolayer resistance and impedance.
  • ZEB1 knockdown led to decreased YES tyrosine kinase expression and altered YAP1 expression and localization.
  • Silencing YAP1 recapitulated ZEB1 knockdown phenotypes, including reduced VE-cadherin phosphorylation and impaired barrier integrity.

Conclusions:

  • ZEB1 plays a role in maintaining lymphatic endothelial barrier integrity.
  • ZEB1 influences lymphatic barrier function through modulation of YAP1 and YES signaling pathways.
  • ZEB1 contributes to lymphatic endothelial barrier maintenance by affecting VE-cadherin phosphorylation and localization.