Environmental Ligands of the Aryl Hydrocarbon Receptor and Their Effects in Models of Adult Liver Progenitor Cells
The toxicity of environmental and dietary ligands of the aryl hydrocarbon receptor (AhR) in mature liver parenchymal cells is well appreciated, while considerably less attention has been paid to their impact on cell populations exhibiting phenotypic features of liver progenitor cells. Here, we discu...
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Online Access: | http://dx.doi.org/10.1155/2016/4326194 |
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doaj-5530f7e928e54fa5abbfa3b9406e94772020-11-24T22:43:32ZengHindawi LimitedStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/43261944326194Environmental Ligands of the Aryl Hydrocarbon Receptor and Their Effects in Models of Adult Liver Progenitor CellsJan Vondráček0Miroslav Machala1Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, 61265 Brno, Czech RepublicDepartment of Chemistry and Toxicology, Veterinary Research Institute, 62100 Brno, Czech RepublicThe toxicity of environmental and dietary ligands of the aryl hydrocarbon receptor (AhR) in mature liver parenchymal cells is well appreciated, while considerably less attention has been paid to their impact on cell populations exhibiting phenotypic features of liver progenitor cells. Here, we discuss the results suggesting that the consequences of the AhR activation in the cellular models derived from bipotent liver progenitors could markedly differ from those in hepatocytes. In contact-inhibited liver progenitor cells, the AhR agonists induce a range of effects potentially linked with tumor promotion. They can stimulate cell cycle progression/proliferation and deregulate cell-to-cell communication, which is associated with downregulation of proteins forming gap junctions, adherens junctions, and desmosomes (such as connexin 43, E-cadherin, β-catenin, and plakoglobin), as well as with reduced cell adhesion and inhibition of intercellular communication. At the same time, toxic AhR ligands may affect the activity of the signaling pathways contributing to regulation of liver progenitor cell activation and/or differentiation, such as downregulation of Wnt/β-catenin and TGF-β signaling, or upregulation of transcriptional targets of YAP/TAZ, the effectors of Hippo signaling pathway. These data illustrate the need to better understand the potential role of liver progenitors in the AhR-mediated liver carcinogenesis and tumor promotion.http://dx.doi.org/10.1155/2016/4326194 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jan Vondráček Miroslav Machala |
spellingShingle |
Jan Vondráček Miroslav Machala Environmental Ligands of the Aryl Hydrocarbon Receptor and Their Effects in Models of Adult Liver Progenitor Cells Stem Cells International |
author_facet |
Jan Vondráček Miroslav Machala |
author_sort |
Jan Vondráček |
title |
Environmental Ligands of the Aryl Hydrocarbon Receptor and Their Effects in Models of Adult Liver Progenitor Cells |
title_short |
Environmental Ligands of the Aryl Hydrocarbon Receptor and Their Effects in Models of Adult Liver Progenitor Cells |
title_full |
Environmental Ligands of the Aryl Hydrocarbon Receptor and Their Effects in Models of Adult Liver Progenitor Cells |
title_fullStr |
Environmental Ligands of the Aryl Hydrocarbon Receptor and Their Effects in Models of Adult Liver Progenitor Cells |
title_full_unstemmed |
Environmental Ligands of the Aryl Hydrocarbon Receptor and Their Effects in Models of Adult Liver Progenitor Cells |
title_sort |
environmental ligands of the aryl hydrocarbon receptor and their effects in models of adult liver progenitor cells |
publisher |
Hindawi Limited |
series |
Stem Cells International |
issn |
1687-966X 1687-9678 |
publishDate |
2016-01-01 |
description |
The toxicity of environmental and dietary ligands of the aryl hydrocarbon receptor (AhR) in mature liver parenchymal cells is well appreciated, while considerably less attention has been paid to their impact on cell populations exhibiting phenotypic features of liver progenitor cells. Here, we discuss the results suggesting that the consequences of the AhR activation in the cellular models derived from bipotent liver progenitors could markedly differ from those in hepatocytes. In contact-inhibited liver progenitor cells, the AhR agonists induce a range of effects potentially linked with tumor promotion. They can stimulate cell cycle progression/proliferation and deregulate cell-to-cell communication, which is associated with downregulation of proteins forming gap junctions, adherens junctions, and desmosomes (such as connexin 43, E-cadherin, β-catenin, and plakoglobin), as well as with reduced cell adhesion and inhibition of intercellular communication. At the same time, toxic AhR ligands may affect the activity of the signaling pathways contributing to regulation of liver progenitor cell activation and/or differentiation, such as downregulation of Wnt/β-catenin and TGF-β signaling, or upregulation of transcriptional targets of YAP/TAZ, the effectors of Hippo signaling pathway. These data illustrate the need to better understand the potential role of liver progenitors in the AhR-mediated liver carcinogenesis and tumor promotion. |
url |
http://dx.doi.org/10.1155/2016/4326194 |
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