Site-1 protease-mediated cholesterol metabolism is essential for lymphatic development in mice.

ABSTRACT: Recent evidence suggests that cellular metabolism, including glycolysis and fatty acid synthesis in lymphatic endothelial cells (LECs), plays essential roles in developing functional lymphatic systems. Site-1 protease (S1P) proteolytically activates membrane-bound latent transcription factor sterol regulatory element-binding proteins (SREBPs), which are required to induce lipid biosynthesis. In this study, we generated mice with pan-endothelial or LEC-specific deficiency of either S1P or SREBP2. Mouse embryos with pan-endothelial deletion of S1P showed defective lymphatic vessel migration in skin and lymphedema, while their blood vasculature formation was relatively normal. Mice lacking S1P in LECs or SREBP2 in LECs exhibited chylous ascites, reduced lipogenic gene expression, and reduced

SUBMITTER: Kondo Y 

PROVIDER: S-EPMC12581667 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature