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Differential regulation of hepatic physiology and injury by the TAM receptors Axl and Mer
Genome-wide association studies have implicated the TAM receptor tyrosine kinase (RTK) Mer in liver disease, yet our understanding of the role that Mer and its related RTKs Tyro3 and Axl play in liver homeostasis and the response to acute injury is limited. We find that Mer and Axl are most prominen...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335405/ https://www.ncbi.nlm.nih.gov/pubmed/32571802 http://dx.doi.org/10.26508/lsa.202000694 |
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author | Zagórska, Anna Través, Paqui G Jiménez-García, Lidia Strickland, Jenna D Oh, Joanne Tapia, Francisco J Mayoral, Rafael Burrola, Patrick Copple, Bryan L Lemke, Greg |
author_facet | Zagórska, Anna Través, Paqui G Jiménez-García, Lidia Strickland, Jenna D Oh, Joanne Tapia, Francisco J Mayoral, Rafael Burrola, Patrick Copple, Bryan L Lemke, Greg |
author_sort | Zagórska, Anna |
collection | PubMed |
description | Genome-wide association studies have implicated the TAM receptor tyrosine kinase (RTK) Mer in liver disease, yet our understanding of the role that Mer and its related RTKs Tyro3 and Axl play in liver homeostasis and the response to acute injury is limited. We find that Mer and Axl are most prominently expressed in hepatic Kupffer and endothelial cells and that as mice lacking these RTKs age, they develop profound liver disease characterized by apoptotic cell accumulation and immune activation. We further find that Mer is critical to the phagocytosis of apoptotic hepatocytes generated in settings of acute hepatic injury, and that Mer and Axl act in concert to inhibit cytokine production in these settings. In contrast, we find that Axl is uniquely important in mitigating liver damage during acetaminophen intoxication. Although Mer and Axl are protective in acute injury models, we find that Axl exacerbates fibrosis in a model of chronic injury. These divergent effects have important implications for the design and implementation of TAM-directed therapeutics that might target these RTKs in the liver. |
format | Online Article Text |
id | pubmed-7335405 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-73354052020-07-15 Differential regulation of hepatic physiology and injury by the TAM receptors Axl and Mer Zagórska, Anna Través, Paqui G Jiménez-García, Lidia Strickland, Jenna D Oh, Joanne Tapia, Francisco J Mayoral, Rafael Burrola, Patrick Copple, Bryan L Lemke, Greg Life Sci Alliance Research Articles Genome-wide association studies have implicated the TAM receptor tyrosine kinase (RTK) Mer in liver disease, yet our understanding of the role that Mer and its related RTKs Tyro3 and Axl play in liver homeostasis and the response to acute injury is limited. We find that Mer and Axl are most prominently expressed in hepatic Kupffer and endothelial cells and that as mice lacking these RTKs age, they develop profound liver disease characterized by apoptotic cell accumulation and immune activation. We further find that Mer is critical to the phagocytosis of apoptotic hepatocytes generated in settings of acute hepatic injury, and that Mer and Axl act in concert to inhibit cytokine production in these settings. In contrast, we find that Axl is uniquely important in mitigating liver damage during acetaminophen intoxication. Although Mer and Axl are protective in acute injury models, we find that Axl exacerbates fibrosis in a model of chronic injury. These divergent effects have important implications for the design and implementation of TAM-directed therapeutics that might target these RTKs in the liver. Life Science Alliance LLC 2020-06-22 /pmc/articles/PMC7335405/ /pubmed/32571802 http://dx.doi.org/10.26508/lsa.202000694 Text en © 2020 Zagórska et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Zagórska, Anna Través, Paqui G Jiménez-García, Lidia Strickland, Jenna D Oh, Joanne Tapia, Francisco J Mayoral, Rafael Burrola, Patrick Copple, Bryan L Lemke, Greg Differential regulation of hepatic physiology and injury by the TAM receptors Axl and Mer |
title | Differential regulation of hepatic physiology and injury by the TAM receptors Axl and Mer |
title_full | Differential regulation of hepatic physiology and injury by the TAM receptors Axl and Mer |
title_fullStr | Differential regulation of hepatic physiology and injury by the TAM receptors Axl and Mer |
title_full_unstemmed | Differential regulation of hepatic physiology and injury by the TAM receptors Axl and Mer |
title_short | Differential regulation of hepatic physiology and injury by the TAM receptors Axl and Mer |
title_sort | differential regulation of hepatic physiology and injury by the tam receptors axl and mer |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335405/ https://www.ncbi.nlm.nih.gov/pubmed/32571802 http://dx.doi.org/10.26508/lsa.202000694 |
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