Imbalanced Activation of Wnt-/β-Catenin-Signaling in Liver Endothelium Alters Normal Sinusoidal Differentiation

• DOI: 10.3389/fphys.2021.722394
• Publication Date: 2021-09-29T06:48:44Z
• Authors: Philipp-Sebastian...; Kajetan Sandorski; Joschka Heil; Christian D. Schmid; Sina W. Kürschner; Johannes Hoffmann; Manuel Winkler; Theresa Staniczek; Carolina de la Torre; Carsten Sticht; Kai Schledzewski; Makoto Mark Taketo; Felix A. Trogisch; Joerg Heineke; Cyrill Géraud; Sergij Goerdt; Victor Olsavszky
• Keywords: 0301 basic medicine; 03 medical and health sciences; mice; liver sinusoidal endothelial cells; Physiology; QP1-981; liver; triglycerides; endothelial cells; 3. Good health

Endothelial wingless-related integration site (Wnt)-/β-catenin signaling is a key regulator of the tightly sealed blood–brain barrier. In hepatic vascular niche angiokine-mediated Wnt was recently identified as an important hepatocyte function, including determination final adult liver size, regeneration, and metabolic zonation. Within vasculature, sinusoidal endothelial cells (LSECs) are morphologically unique functionally specialized microvascular (ECs). Pathological changes LSECs involved in chronic diseases, hepatocarcinogenesis, metastasis. To comprehensively analyze effects Wnt-/β-catenin liver, we used subtype-specific Clec4g-iCre mice to generate ECs with overexpression Ctnnb1. resultant tg / wt ;Ctnnb1(Ex3) fl ( Ctnnb1 OE − EC ) mice, activation resulted transdifferentiation disturbed zonation, that is, loss midzonal LSEC marker lymphatic vessel hyaluronic acid receptor 1 (Lyve1) enrichment continuous genes, such cluster differentiation (CD)34 Apln . Notably, gene set analysis revealed overrepresentation brain transcripts. Activation did not induce fibrosis or alter but exhibited significantly increased plasma triglyceride concentrations, while lipid content slightly reduced. arterial heart has been reported previously cause cardiomyopathy. As active subset cardiac ECs, it unexpected showed reduced overall survival dysfunction. Altogether, balanced required for normal maintenance levels.