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

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...

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Main Authors: Ruihua Ma, Angelica S Martínez-Ramírez, Thomas L Borders, Fanding Gao, Beatriz Sosa-Pineda
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2020-03-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/46206
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author Ruihua Ma
Angelica S Martínez-Ramírez
Thomas L Borders
Fanding Gao
Beatriz Sosa-Pineda
author_facet Ruihua Ma
Angelica S Martínez-Ramírez
Thomas L Borders
Fanding Gao
Beatriz Sosa-Pineda
author_sort Ruihua Ma
collection DOAJ
description 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.
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spelling doaj.art-28de306127df4f968f04634f054f2d572022-12-22T03:37:47ZengeLife Sciences Publications LtdeLife2050-084X2020-03-01910.7554/eLife.46206Metabolic and non-metabolic liver zonation is established non-synchronously and requires sinusoidal WntsRuihua Ma0Angelica S Martínez-Ramírez1Thomas L Borders2Fanding Gao3Beatriz Sosa-Pineda4https://orcid.org/0000-0001-6872-5444Feinberg Cardiovascular and Renal Research Institute, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United StatesFeinberg Cardiovascular and Renal Research Institute, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United StatesFeinberg Cardiovascular and Renal Research Institute, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United StatesFeinberg Cardiovascular and Renal Research Institute, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United StatesFeinberg Cardiovascular and Renal Research Institute, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United StatesThe 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.https://elifesciences.org/articles/46206hepatic zonationClaudin-2Wnthepatic sinusoidscarbon tetrachloride
spellingShingle Ruihua Ma
Angelica S Martínez-Ramírez
Thomas L Borders
Fanding Gao
Beatriz Sosa-Pineda
Metabolic and non-metabolic liver zonation is established non-synchronously and requires sinusoidal Wnts
eLife
hepatic zonation
Claudin-2
Wnt
hepatic sinusoids
carbon tetrachloride
title Metabolic and non-metabolic liver zonation is established non-synchronously and requires sinusoidal Wnts
title_full Metabolic and non-metabolic liver zonation is established non-synchronously and requires sinusoidal Wnts
title_fullStr Metabolic and non-metabolic liver zonation is established non-synchronously and requires sinusoidal Wnts
title_full_unstemmed Metabolic and non-metabolic liver zonation is established non-synchronously and requires sinusoidal Wnts
title_short Metabolic and non-metabolic liver zonation is established non-synchronously and requires sinusoidal Wnts
title_sort metabolic and non metabolic liver zonation is established non synchronously and requires sinusoidal wnts
topic hepatic zonation
Claudin-2
Wnt
hepatic sinusoids
carbon tetrachloride
url https://elifesciences.org/articles/46206
work_keys_str_mv AT ruihuama metabolicandnonmetabolicliverzonationisestablishednonsynchronouslyandrequiressinusoidalwnts
AT angelicasmartinezramirez metabolicandnonmetabolicliverzonationisestablishednonsynchronouslyandrequiressinusoidalwnts
AT thomaslborders metabolicandnonmetabolicliverzonationisestablishednonsynchronouslyandrequiressinusoidalwnts
AT fandinggao metabolicandnonmetabolicliverzonationisestablishednonsynchronouslyandrequiressinusoidalwnts
AT beatrizsosapineda metabolicandnonmetabolicliverzonationisestablishednonsynchronouslyandrequiressinusoidalwnts