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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Format: | Article |
Language: | English |
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eLife Sciences Publications Ltd
2020-03-01
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Series: | eLife |
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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. |
first_indexed | 2024-04-12T09:52:49Z |
format | Article |
id | doaj.art-28de306127df4f968f04634f054f2d57 |
institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-04-12T09:52:49Z |
publishDate | 2020-03-01 |
publisher | eLife Sciences Publications Ltd |
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series | eLife |
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 |
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