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Life Cycle Analysis of Kidney Gene Expression in Male F344 Rats

Age is a predisposing condition for susceptibility to chronic kidney disease and progression as well as acute kidney injury that may arise due to the adverse effects of some drugs. Age-related differences in kidney biology, therefore, are a key concern in understanding drug safety and disease progre...

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Autores principales: Kwekel, Joshua C., Desai, Varsha G., Moland, Carrie L., Vijay, Vikrant, Fuscoe, James C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792073/
https://www.ncbi.nlm.nih.gov/pubmed/24116033
http://dx.doi.org/10.1371/journal.pone.0075305
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author Kwekel, Joshua C.
Desai, Varsha G.
Moland, Carrie L.
Vijay, Vikrant
Fuscoe, James C.
author_facet Kwekel, Joshua C.
Desai, Varsha G.
Moland, Carrie L.
Vijay, Vikrant
Fuscoe, James C.
author_sort Kwekel, Joshua C.
collection PubMed
description Age is a predisposing condition for susceptibility to chronic kidney disease and progression as well as acute kidney injury that may arise due to the adverse effects of some drugs. Age-related differences in kidney biology, therefore, are a key concern in understanding drug safety and disease progression. We hypothesize that the underlying suite of genes expressed in the kidney at various life cycle stages will impact susceptibility to adverse drug reactions. Therefore, establishing changes in baseline expression data between these life stages is the first and necessary step in evaluating this hypothesis. Untreated male F344 rats were sacrificed at 2, 5, 6, 8, 15, 21, 78, and 104 weeks of age. Kidneys were collected for histology and gene expression analysis. Agilent whole-genome rat microarrays were used to query global expression profiles. An ANOVA (p<0.01) coupled with a fold-change>1.5 in relative mRNA expression, was used to identify 3,724 unique differentially expressed genes (DEGs). Principal component analyses of these DEGs revealed three major divisions in life-cycle renal gene expression. K-means cluster analysis identified several groups of genes that shared age-specific patterns of expression. Pathway analysis of these gene groups revealed age-specific gene networks and functions related to renal function and aging, including extracellular matrix turnover, immune cell response, and renal tubular injury. Large age-related changes in expression were also demonstrated for the genes that code for qualified renal injury biomarkers KIM-1, Clu, and Tff3. These results suggest specific groups of genes that may underlie age-specific susceptibilities to adverse drug reactions and disease. This analysis of the basal gene expression patterns of renal genes throughout the life cycle of the rat will improve the use of current and future renal biomarkers and inform our assessments of kidney injury and disease.
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spelling pubmed-37920732013-10-10 Life Cycle Analysis of Kidney Gene Expression in Male F344 Rats Kwekel, Joshua C. Desai, Varsha G. Moland, Carrie L. Vijay, Vikrant Fuscoe, James C. PLoS One Research Article Age is a predisposing condition for susceptibility to chronic kidney disease and progression as well as acute kidney injury that may arise due to the adverse effects of some drugs. Age-related differences in kidney biology, therefore, are a key concern in understanding drug safety and disease progression. We hypothesize that the underlying suite of genes expressed in the kidney at various life cycle stages will impact susceptibility to adverse drug reactions. Therefore, establishing changes in baseline expression data between these life stages is the first and necessary step in evaluating this hypothesis. Untreated male F344 rats were sacrificed at 2, 5, 6, 8, 15, 21, 78, and 104 weeks of age. Kidneys were collected for histology and gene expression analysis. Agilent whole-genome rat microarrays were used to query global expression profiles. An ANOVA (p<0.01) coupled with a fold-change>1.5 in relative mRNA expression, was used to identify 3,724 unique differentially expressed genes (DEGs). Principal component analyses of these DEGs revealed three major divisions in life-cycle renal gene expression. K-means cluster analysis identified several groups of genes that shared age-specific patterns of expression. Pathway analysis of these gene groups revealed age-specific gene networks and functions related to renal function and aging, including extracellular matrix turnover, immune cell response, and renal tubular injury. Large age-related changes in expression were also demonstrated for the genes that code for qualified renal injury biomarkers KIM-1, Clu, and Tff3. These results suggest specific groups of genes that may underlie age-specific susceptibilities to adverse drug reactions and disease. This analysis of the basal gene expression patterns of renal genes throughout the life cycle of the rat will improve the use of current and future renal biomarkers and inform our assessments of kidney injury and disease. Public Library of Science 2013-10-07 /pmc/articles/PMC3792073/ /pubmed/24116033 http://dx.doi.org/10.1371/journal.pone.0075305 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Kwekel, Joshua C.
Desai, Varsha G.
Moland, Carrie L.
Vijay, Vikrant
Fuscoe, James C.
Life Cycle Analysis of Kidney Gene Expression in Male F344 Rats
title Life Cycle Analysis of Kidney Gene Expression in Male F344 Rats
title_full Life Cycle Analysis of Kidney Gene Expression in Male F344 Rats
title_fullStr Life Cycle Analysis of Kidney Gene Expression in Male F344 Rats
title_full_unstemmed Life Cycle Analysis of Kidney Gene Expression in Male F344 Rats
title_short Life Cycle Analysis of Kidney Gene Expression in Male F344 Rats
title_sort life cycle analysis of kidney gene expression in male f344 rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792073/
https://www.ncbi.nlm.nih.gov/pubmed/24116033
http://dx.doi.org/10.1371/journal.pone.0075305
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