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  • Metabolic and non-metabolic liver zonation is established non-synchronously and requires sinusoidal Wnts.

Metabolic and non-metabolic liver zonation is established non-synchronously and requires sinusoidal Wnts.

eLife (2020-03-11)
Ruihua Ma, Angelica S Martínez-Ramírez, Thomas L Borders, Fanding Gao, Beatriz Sosa-Pineda
ABSTRACT

The distribution of complementary metabolic functions in hepatocytes along a portocentral axis is called liver zonation. Endothelial secreted Wnt ligands maintain metabolic zonation in the adult murine liver but whether those ligands are necessary to initiate zonation in the immature liver has been only partially explored. Also, numerous non-metabolic proteins display zonated expression in the adult liver but it is not entirely clear if their localization requires endothelial Wnts. Here we used a novel transgenic mouse model to compare the spatial distribution of zonated non-metabolic proteins with that of typical zonated metabolic enzymes during liver maturation and after acute injury induced by carbon tetrachloride (CCl4). We also investigated how preventing Wnt ligand secretion from endothelial cells affects zonation patterns under homeostasis and after acute injury. Our study demonstrates that metabolic and non-metabolic zonation are established non-synchronously during maturation and regeneration and require multiple endothelial Wnt sources.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Carbon tetrachloride, reagent grade, 99.9%
Sigma-Aldrich
Corn oil, delivery vehicle for fat-soluble compounds
Sigma-Aldrich
ALT Activity Assay, sufficient for 100 colorimetric or fluorometric tests
Sigma-Aldrich
Dexamethasone, powder, BioReagent, suitable for cell culture, ≥97%