Publication Date
5-25-2016
Date of Final Oral Examination (Defense)
4-22-2016
Type of Culminating Activity
Dissertation
Degree Title
Doctor of Philosophy in Biomolecular Sciences
Department
Biology
Supervisory Committee Chair
Kristen A. Mitchell, Ph.D.
Supervisory Committee Member
Allan Albig, Ph.D.
Supervisory Committee Member
Kenneth A. Cornell, Ph.D.
Supervisory Committee Member
Daniel Fologea, Ph.D.
Supervisory Committee Member
Julia Thom Oxford, Ph.D.
Abstract
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental pollutant and high-affinity ligand for the aryl hydrocarbon receptor (AhR). Exposure to TCDD elicits a spectrum of toxic effects, many involving aberrant cell proliferation, activation, and differentiation. The liver is a target organ for TCDD toxicity, and increasing evidence indicates that AhR signaling regulates genes that coordinate deposition and remodeling of the extracellular matrix (ECM) in the liver. Hepatic stellate cells (HSCs) are central to ECM remodeling in the liver. We recently reported that TCDD treatment increases the activation of human HSCs in vitro. The goal of this study was to determine if TCDD increases HSC activation in vivo using a mouse model of experimental liver fibrosis and to determine the consequences of TCDD treatment on ECM remodeling. To elicit fibrosis, C57BL6/ male mice were treated twice weekly for 8 weeks with 0.5 ml/kg carbon tetrachloride (CCl4). TCDD (20 mg/kg) was administered once a week during weeks 7 and 8. Results indicate that TCDD increased liver damage in CCl4-treated mice and increased activation of HSCs. However, TCDD treatment did not increase collagen deposition in the liver, nor did it exacerbate fibrosis. Instead, TCDD modulated expression and activity of ECM remodeling molecules associated with enhanced matrix turnover. These results support the hypothesis that TCDD increases HSC activation in vivo, and modulates ECM remodeling in response to chronic liver injury.
Recommended Citation
Lamb, Cheri Lou, "Consequences of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) on Hepatic Stellate Cell Activation and Extracellular Matrix Remodeling During Chronic Liver Injury" (2016). Boise State University Theses and Dissertations. 1114.
https://scholarworks.boisestate.edu/td/1114