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  • The β-catenin C terminus links Wnt and sphingosine-1-phosphate signaling pathways to promote vascular remodeling and atherosclerosis.

The β-catenin C terminus links Wnt and sphingosine-1-phosphate signaling pathways to promote vascular remodeling and atherosclerosis.

Science advances (2024-03-13)
Gustavo H Oliveira-Paula, Sophia Liu, Alishba Maira, Gaia Ressa, Graziele C Ferreira, Amado Quintar, Smitha Jayakumar, Vanessa Almonte, Dippal Parikh, Tomas Valenta, Konrad Basler, Timothy Hla, Dario F Riascos-Bernal, Nicholas E S Sibinga
ABSTRACT

Canonical Wnt and sphingosine-1-phosphate (S1P) signaling pathways are highly conserved systems that contribute to normal vertebrate development, with key consequences for immune, nervous, and cardiovascular system function; despite these functional overlaps, little is known about Wnt/β-catenin-S1P cross-talk. In the vascular system, both Wnt/β-catenin and S1P signals affect vessel maturation, stability, and barrier function, but information regarding their potential coordination is scant. We report an instance of functional interaction between the two pathways, including evidence that S1P receptor 1 (S1PR1) is a transcriptional target of β-catenin. By studying vascular smooth muscle cells and arterial injury response, we find a specific requirement for the β-catenin carboxyl terminus, which acts to induce S1PR1, and show that this interaction is essential for vascular remodeling. We also report that pharmacological inhibition of the β-catenin carboxyl terminus reduces S1PR1 expression, neointima formation, and atherosclerosis. These findings provide mechanistic understanding of how Wnt/β-catenin and S1P systems collaborate during vascular remodeling and inform strategies for therapeutic manipulation.

MATERIALS
Product Number
Brand
Product Description

Roche
cOmplete, Mini, EDTA-free Protease Inhibitor Cocktail, Tablets provided in EASYpacks
Sigma-Aldrich
Anti-Sphingosine 1-phosphate receptor 1 (S1P1) Antibody, clone 8B7.1, clone 8B7.1, from mouse