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Aryl Hydrocarbon Receptor Activation by TCDD Modulates Expression of Extracellular Matrix Remodeling Genes during Experimental Liver Fibrosis

The aryl hydrocarbon receptor (AhR) is a soluble, ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Increasing evidence implicates the AhR in regulating extracellular matrix (ECM) homeostasis. We recently reported that TCDD increased necr...

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Autores principales: Lamb, Cheri L., Cholico, Giovan N., Perkins, Daniel E., Fewkes, Michael T., Oxford, Julia Thom, Lujan, Trevor J., Morrill, Erica E., Mitchell, Kristen A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031815/
https://www.ncbi.nlm.nih.gov/pubmed/27672655
http://dx.doi.org/10.1155/2016/5309328
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author Lamb, Cheri L.
Cholico, Giovan N.
Perkins, Daniel E.
Fewkes, Michael T.
Oxford, Julia Thom
Lujan, Trevor J.
Morrill, Erica E.
Mitchell, Kristen A.
author_facet Lamb, Cheri L.
Cholico, Giovan N.
Perkins, Daniel E.
Fewkes, Michael T.
Oxford, Julia Thom
Lujan, Trevor J.
Morrill, Erica E.
Mitchell, Kristen A.
author_sort Lamb, Cheri L.
collection PubMed
description The aryl hydrocarbon receptor (AhR) is a soluble, ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Increasing evidence implicates the AhR in regulating extracellular matrix (ECM) homeostasis. We recently reported that TCDD increased necroinflammation and myofibroblast activation during liver injury elicited by carbon tetrachloride (CCl(4)). However, TCDD did not increase collagen deposition or exacerbate fibrosis in CCl(4)-treated mice, which raises the possibility that TCDD may enhance ECM turnover. The goal of this study was to determine how TCDD impacts ECM remodeling gene expression in the liver. Male C57BL/6 mice were treated for 8 weeks with 0.5 mL/kg CCl(4), and TCDD (20 μg/kg) was administered during the last two weeks. Results indicate that TCDD increased mRNA levels of procollagen types I, III, IV, and VI and the collagen processing molecules HSP47 and lysyl oxidase. TCDD also increased gelatinase activity and mRNA levels of matrix metalloproteinase- (MMP-) 3, MMP-8, MMP-9, and MMP-13. Furthermore, TCDD modulated expression of genes in the plasminogen activator/plasmin system, which regulates MMP activation, and it also increased TIMP1 gene expression. These findings support the notion that AhR activation by TCDD dysregulates ECM remodeling gene expression and may facilitate ECM metabolism despite increased liver injury.
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spelling pubmed-50318152016-09-26 Aryl Hydrocarbon Receptor Activation by TCDD Modulates Expression of Extracellular Matrix Remodeling Genes during Experimental Liver Fibrosis Lamb, Cheri L. Cholico, Giovan N. Perkins, Daniel E. Fewkes, Michael T. Oxford, Julia Thom Lujan, Trevor J. Morrill, Erica E. Mitchell, Kristen A. Biomed Res Int Research Article The aryl hydrocarbon receptor (AhR) is a soluble, ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Increasing evidence implicates the AhR in regulating extracellular matrix (ECM) homeostasis. We recently reported that TCDD increased necroinflammation and myofibroblast activation during liver injury elicited by carbon tetrachloride (CCl(4)). However, TCDD did not increase collagen deposition or exacerbate fibrosis in CCl(4)-treated mice, which raises the possibility that TCDD may enhance ECM turnover. The goal of this study was to determine how TCDD impacts ECM remodeling gene expression in the liver. Male C57BL/6 mice were treated for 8 weeks with 0.5 mL/kg CCl(4), and TCDD (20 μg/kg) was administered during the last two weeks. Results indicate that TCDD increased mRNA levels of procollagen types I, III, IV, and VI and the collagen processing molecules HSP47 and lysyl oxidase. TCDD also increased gelatinase activity and mRNA levels of matrix metalloproteinase- (MMP-) 3, MMP-8, MMP-9, and MMP-13. Furthermore, TCDD modulated expression of genes in the plasminogen activator/plasmin system, which regulates MMP activation, and it also increased TIMP1 gene expression. These findings support the notion that AhR activation by TCDD dysregulates ECM remodeling gene expression and may facilitate ECM metabolism despite increased liver injury. Hindawi Publishing Corporation 2016 2016-09-08 /pmc/articles/PMC5031815/ /pubmed/27672655 http://dx.doi.org/10.1155/2016/5309328 Text en Copyright © 2016 Cheri L. Lamb et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Lamb, Cheri L.
Cholico, Giovan N.
Perkins, Daniel E.
Fewkes, Michael T.
Oxford, Julia Thom
Lujan, Trevor J.
Morrill, Erica E.
Mitchell, Kristen A.
Aryl Hydrocarbon Receptor Activation by TCDD Modulates Expression of Extracellular Matrix Remodeling Genes during Experimental Liver Fibrosis
title Aryl Hydrocarbon Receptor Activation by TCDD Modulates Expression of Extracellular Matrix Remodeling Genes during Experimental Liver Fibrosis
title_full Aryl Hydrocarbon Receptor Activation by TCDD Modulates Expression of Extracellular Matrix Remodeling Genes during Experimental Liver Fibrosis
title_fullStr Aryl Hydrocarbon Receptor Activation by TCDD Modulates Expression of Extracellular Matrix Remodeling Genes during Experimental Liver Fibrosis
title_full_unstemmed Aryl Hydrocarbon Receptor Activation by TCDD Modulates Expression of Extracellular Matrix Remodeling Genes during Experimental Liver Fibrosis
title_short Aryl Hydrocarbon Receptor Activation by TCDD Modulates Expression of Extracellular Matrix Remodeling Genes during Experimental Liver Fibrosis
title_sort aryl hydrocarbon receptor activation by tcdd modulates expression of extracellular matrix remodeling genes during experimental liver fibrosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031815/
https://www.ncbi.nlm.nih.gov/pubmed/27672655
http://dx.doi.org/10.1155/2016/5309328
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