p73 is required for vessel integrity controlling endothelial junctional dynamics through Angiomotin

Area of Science:

• Vascular Biology
• Molecular Biology
• Cell Biology

Background:

• Endothelial junction integrity is crucial for physiological function and organ health.
• Mechanisms governing endothelial cell junction assembly are not fully understood.
• TAp73 is a transcription factor with potential roles in vascular development.

Purpose of the Study:

• To investigate the role of TAp73 in endothelial junction formation and blood vessel morphogenesis.
• To identify downstream targets of TAp73 in vascular endothelial cells.
• To elucidate the TAp73-Angiomotin (AMOT)/Yes-associated protein (YAP) signaling axis in maintaining vascular integrity.

Main Methods:

• Knockdown of p73 in human endothelial cells.
• Analysis of Angiomotin expression and localization.
• Assessment of adherens junction morphology and barrier permeability.
• In vivo studies using p73-knockout mouse retinas.

Main Results:

• TAp73 knockdown decreased Angiomotin expression and altered junctional morphology, increasing serrated junctions and stress fibers.
• Defects in endothelial monolayer integrity, hyperpermeability, and reduced transendothelial electric resistance were observed.
• p73-knockout retinas exhibited defective sprout morphology and hemorrhages, indicating in vivo relevance.
• Stabilization of Angiomotin levels rescued junctional defects.

Conclusions:

• TAp73 functions as a vascular architect, orchestrating transcriptional programs for endothelial junction establishment.
• TAp73 regulates vascular integrity, at least partly, through Angiomotin and its downstream signaling.
• TAp73 plays a critical role in maintaining blood vessel integrity in vivo during development and angiogenesis.