RSPO3 impairs barrier function of human vascular endothelial monolayers and synergizes with pro-inflammatory IL-1

Area of Science:

• Vascular Biology
• Cell Biology
• Inflammation Research

Background:

• Endothelial barrier dysfunction, marked by hyperpermeability, is central to chronic inflammatory diseases.
• Mediators from immune cells and endothelium can compromise vascular barrier integrity.
• The role of matricellular protein RSPO3 in regulating endothelial barrier function was previously unknown.

Purpose of the Study:

• To investigate the impact of RSPO3 on the barrier function of human macro- and micro-vascular endothelial cells.
• To determine if RSPO3 alone or with IL-1β affects endothelial permeability.
• To elucidate the molecular mechanisms underlying RSPO3-induced endothelial barrier changes.

Main Methods:

• Primary human endothelial cells from various vascular beds were cultured.
• Cells were treated with RSPO3, IL-1β, or both.
• Endothelial barrier function was assessed non-invasively using Electric Cell-substrate Impedance Sensing (ECIS).

Main Results:

• RSPO3 treatment significantly increased permeability in all tested endothelial monolayers.
• RSPO3 induced gaps between endothelial cells by disrupting adherens junctions (β-catenin/VE-cadherin).
• RSPO3 potentiated the barrier-disrupting effects of IL-1β.

Conclusions:

• RSPO3 acts as a mediator of endothelial hyperpermeability.
• RSPO3 synergizes with the inflammatory cytokine IL-1β to impair endothelial barrier function.
• Further research is needed to understand RSPO3's role in chronic inflammatory diseases.