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

Authors

Cheri L. Lamb, Boise State University
Giovan Cholico, Boise State University
Daniel E. Perkins, Boise State University
Michael T. Fewkes, Boise State University
Julia T. Oxford, Boise State UniversityFollow
Trevor J. Lujan, Boise State UniversityFollow
Erica E. Morrill, Boise State UniversityFollow
Kristen A. Mitchell, Boise State University

Document Type

Article

Publication Date

2016

DOI

http://dx.doi.org/10.1155/2016/5309328

Abstract

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 (CCl₄).However, TCDD did not increase collagen deposition or exacerbate fibrosis in CCl₄-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 CCl₄, 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.

Copyright Statement

This document was originally published in BioMed Research International by the Hindawi Publishing Corporation. This work is provided under a Creative Commons Attribution 4.0 license. Details regarding the use of this work can be found at: http://creativecommons.org/licenses/by/4.0/. doi: 10.1155/2016/5309328

Publication Information

Lamb, Cheri L.; Cholico, Giovan; Perkins, Daniel E.; Fewkes, Michael T.; Oxford, Julia T.; Lujan, Trevor J.; Morrill, Erica E.; and Mitchell, Kristen A.. (2016). "Aryl Hydrocarbon Receptor Activation by TCDD Modulates Expression of Extracellular Matrix Remodeling Genes During Experimental Liver Fibrosis". BioMed Research International, 20165309328-1 - 5309238-14.