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Concordance between Thioacetamide-Induced Liver Injury in Rat and Human In Vitro Gene Expression Data
The immense resources required and the ethical concerns for animal-based toxicological studies have driven the development of in vitro and in silico approaches. Recently, we validated our approach in which the expression of a set of genes is uniquely associated with an organ-injury phenotype (injury...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312807/ https://www.ncbi.nlm.nih.gov/pubmed/32512829 http://dx.doi.org/10.3390/ijms21114017 |
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author | Schyman, Patric Printz, Richard L. Estes, Shanea K. O’Brien, Tracy P. Shiota, Masakazu Wallqvist, Anders |
author_facet | Schyman, Patric Printz, Richard L. Estes, Shanea K. O’Brien, Tracy P. Shiota, Masakazu Wallqvist, Anders |
author_sort | Schyman, Patric |
collection | PubMed |
description | The immense resources required and the ethical concerns for animal-based toxicological studies have driven the development of in vitro and in silico approaches. Recently, we validated our approach in which the expression of a set of genes is uniquely associated with an organ-injury phenotype (injury module), by using thioacetamide, a known liver toxicant. Here, we sought to explore whether RNA-seq data obtained from human cells (in vitro) treated with thioacetamide-S-oxide (a toxic intermediate metabolite) would correlate across species with the injury responses found in rat cells (in vitro) after exposure to this metabolite as well as in rats exposed to thioacetamide (in vivo). We treated two human cell types with thioacetamide-S-oxide (primary hepatocytes with 0 (vehicle), 0.125 (low dose), or 0.25 (high dose) mM, and renal tubular epithelial cells with 0 (vehicle), 0.25 (low dose), or 1.00 (high dose) mM) and collected RNA-seq data 9 or 24 h after treatment. We found that the liver-injury modules significantly altered in human hepatocytes 24 h after high-dose treatment involved cellular infiltration and bile duct proliferation, which are linked to fibrosis. For high-dose treatments, our modular approach predicted the rat in vivo and in vitro results from human in vitro RNA-seq data with Pearson correlation coefficients of 0.60 and 0.63, respectively, which was not observed for individual genes or KEGG pathways. |
format | Online Article Text |
id | pubmed-7312807 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73128072020-06-26 Concordance between Thioacetamide-Induced Liver Injury in Rat and Human In Vitro Gene Expression Data Schyman, Patric Printz, Richard L. Estes, Shanea K. O’Brien, Tracy P. Shiota, Masakazu Wallqvist, Anders Int J Mol Sci Article The immense resources required and the ethical concerns for animal-based toxicological studies have driven the development of in vitro and in silico approaches. Recently, we validated our approach in which the expression of a set of genes is uniquely associated with an organ-injury phenotype (injury module), by using thioacetamide, a known liver toxicant. Here, we sought to explore whether RNA-seq data obtained from human cells (in vitro) treated with thioacetamide-S-oxide (a toxic intermediate metabolite) would correlate across species with the injury responses found in rat cells (in vitro) after exposure to this metabolite as well as in rats exposed to thioacetamide (in vivo). We treated two human cell types with thioacetamide-S-oxide (primary hepatocytes with 0 (vehicle), 0.125 (low dose), or 0.25 (high dose) mM, and renal tubular epithelial cells with 0 (vehicle), 0.25 (low dose), or 1.00 (high dose) mM) and collected RNA-seq data 9 or 24 h after treatment. We found that the liver-injury modules significantly altered in human hepatocytes 24 h after high-dose treatment involved cellular infiltration and bile duct proliferation, which are linked to fibrosis. For high-dose treatments, our modular approach predicted the rat in vivo and in vitro results from human in vitro RNA-seq data with Pearson correlation coefficients of 0.60 and 0.63, respectively, which was not observed for individual genes or KEGG pathways. MDPI 2020-06-04 /pmc/articles/PMC7312807/ /pubmed/32512829 http://dx.doi.org/10.3390/ijms21114017 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Schyman, Patric Printz, Richard L. Estes, Shanea K. O’Brien, Tracy P. Shiota, Masakazu Wallqvist, Anders Concordance between Thioacetamide-Induced Liver Injury in Rat and Human In Vitro Gene Expression Data |
title | Concordance between Thioacetamide-Induced Liver Injury in Rat and Human In Vitro Gene Expression Data |
title_full | Concordance between Thioacetamide-Induced Liver Injury in Rat and Human In Vitro Gene Expression Data |
title_fullStr | Concordance between Thioacetamide-Induced Liver Injury in Rat and Human In Vitro Gene Expression Data |
title_full_unstemmed | Concordance between Thioacetamide-Induced Liver Injury in Rat and Human In Vitro Gene Expression Data |
title_short | Concordance between Thioacetamide-Induced Liver Injury in Rat and Human In Vitro Gene Expression Data |
title_sort | concordance between thioacetamide-induced liver injury in rat and human in vitro gene expression data |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312807/ https://www.ncbi.nlm.nih.gov/pubmed/32512829 http://dx.doi.org/10.3390/ijms21114017 |
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