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The contradictory roles of macrophages in non-alcoholic fatty liver disease and primary liver cancer—Challenges and opportunities

Chronic liver diseases from varying etiologies generally lead to liver fibrosis and cirrhosis. Among them, non-alcoholic fatty liver disease (NAFLD) affects roughly one-quarter of the world population, thus representing a major and increasing public health burden. Chronic hepatocyte injury, inflamma...

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Autores principales: Kohlhepp, Marlene Sophia, Liu, Hanyang, Tacke, Frank, Guillot, Adrien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9950415/
https://www.ncbi.nlm.nih.gov/pubmed/36845555
http://dx.doi.org/10.3389/fmolb.2023.1129831
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author Kohlhepp, Marlene Sophia
Liu, Hanyang
Tacke, Frank
Guillot, Adrien
author_facet Kohlhepp, Marlene Sophia
Liu, Hanyang
Tacke, Frank
Guillot, Adrien
author_sort Kohlhepp, Marlene Sophia
collection PubMed
description Chronic liver diseases from varying etiologies generally lead to liver fibrosis and cirrhosis. Among them, non-alcoholic fatty liver disease (NAFLD) affects roughly one-quarter of the world population, thus representing a major and increasing public health burden. Chronic hepatocyte injury, inflammation (non-alcoholic steatohepatitis, NASH) and liver fibrosis are recognized soils for primary liver cancer, particularly hepatocellular carcinoma (HCC), being the third most common cause for cancer-related deaths worldwide. Despite recent advances in liver disease understanding, therapeutic options on pre-malignant and malignant stages remain limited. Thus, there is an urgent need to identify targetable liver disease-driving mechanisms for the development of novel therapeutics. Monocytes and macrophages comprise a central, yet versatile component of the inflammatory response, fueling chronic liver disease initiation and progression. Recent proteomic and transcriptomic studies performed at singular cell levels revealed a previously overlooked diversity of macrophage subpopulations and functions. Indeed, liver macrophages that encompass liver resident macrophages (also named Kupffer cells) and monocyte-derived macrophages, can acquire a variety of phenotypes depending on microenvironmental cues, and thus exert manifold and sometimes contradictory functions. Those functions range from modulating and exacerbating tissue inflammation to promoting and exaggerating tissue repair mechanisms (i.e., parenchymal regeneration, cancer cell proliferation, angiogenesis, fibrosis). Due to these central functions, liver macrophages represent an attractive target for the treatment of liver diseases. In this review, we discuss the multifaceted and contrary roles of macrophages in chronic liver diseases, with a particular focus on NAFLD/NASH and HCC. Moreover, we discuss potential therapeutic approaches targeting liver macrophages.
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spelling pubmed-99504152023-02-25 The contradictory roles of macrophages in non-alcoholic fatty liver disease and primary liver cancer—Challenges and opportunities Kohlhepp, Marlene Sophia Liu, Hanyang Tacke, Frank Guillot, Adrien Front Mol Biosci Molecular Biosciences Chronic liver diseases from varying etiologies generally lead to liver fibrosis and cirrhosis. Among them, non-alcoholic fatty liver disease (NAFLD) affects roughly one-quarter of the world population, thus representing a major and increasing public health burden. Chronic hepatocyte injury, inflammation (non-alcoholic steatohepatitis, NASH) and liver fibrosis are recognized soils for primary liver cancer, particularly hepatocellular carcinoma (HCC), being the third most common cause for cancer-related deaths worldwide. Despite recent advances in liver disease understanding, therapeutic options on pre-malignant and malignant stages remain limited. Thus, there is an urgent need to identify targetable liver disease-driving mechanisms for the development of novel therapeutics. Monocytes and macrophages comprise a central, yet versatile component of the inflammatory response, fueling chronic liver disease initiation and progression. Recent proteomic and transcriptomic studies performed at singular cell levels revealed a previously overlooked diversity of macrophage subpopulations and functions. Indeed, liver macrophages that encompass liver resident macrophages (also named Kupffer cells) and monocyte-derived macrophages, can acquire a variety of phenotypes depending on microenvironmental cues, and thus exert manifold and sometimes contradictory functions. Those functions range from modulating and exacerbating tissue inflammation to promoting and exaggerating tissue repair mechanisms (i.e., parenchymal regeneration, cancer cell proliferation, angiogenesis, fibrosis). Due to these central functions, liver macrophages represent an attractive target for the treatment of liver diseases. In this review, we discuss the multifaceted and contrary roles of macrophages in chronic liver diseases, with a particular focus on NAFLD/NASH and HCC. Moreover, we discuss potential therapeutic approaches targeting liver macrophages. Frontiers Media S.A. 2023-02-10 /pmc/articles/PMC9950415/ /pubmed/36845555 http://dx.doi.org/10.3389/fmolb.2023.1129831 Text en Copyright © 2023 Kohlhepp, Liu, Tacke and Guillot. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Kohlhepp, Marlene Sophia
Liu, Hanyang
Tacke, Frank
Guillot, Adrien
The contradictory roles of macrophages in non-alcoholic fatty liver disease and primary liver cancer—Challenges and opportunities
title The contradictory roles of macrophages in non-alcoholic fatty liver disease and primary liver cancer—Challenges and opportunities
title_full The contradictory roles of macrophages in non-alcoholic fatty liver disease and primary liver cancer—Challenges and opportunities
title_fullStr The contradictory roles of macrophages in non-alcoholic fatty liver disease and primary liver cancer—Challenges and opportunities
title_full_unstemmed The contradictory roles of macrophages in non-alcoholic fatty liver disease and primary liver cancer—Challenges and opportunities
title_short The contradictory roles of macrophages in non-alcoholic fatty liver disease and primary liver cancer—Challenges and opportunities
title_sort contradictory roles of macrophages in non-alcoholic fatty liver disease and primary liver cancer—challenges and opportunities
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9950415/
https://www.ncbi.nlm.nih.gov/pubmed/36845555
http://dx.doi.org/10.3389/fmolb.2023.1129831
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