Aryl Hydrocarbon Receptor-dependent Liver Development and Hepatotoxicity Are Mediated by Different Cell Types

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2005 Nov 23

PMID 16301529

Citations 128

Authors

Jacqueline A Walisser

Edward Glover

Kalyan Pande

Adam L Liss

Christopher A Bradfield

Affiliations

Soon will be listed here.

Abstract

The aryl hydrocarbon receptor (AHR) plays a role in three areas of biology that include the adaptive metabolism of xenobiotics, the toxic responses associated with exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin), and vascular remodeling of the developing embryo. To test the hypothesis that receptor signaling in different cell types is responsible for these aspects of AHR biology, we generated a conditional Ahr allele where exon 2 is flanked by loxP sites. Through the use of Cre-lox technology, we then investigated the role of AHR signaling in hepatocytes or endothelial cells in mediating prototypical endpoints of adaptive, toxic, or developmental signaling. Using this model, we provide evidence that AHR signaling in endothelial/hematopoietic cells is necessary for developmental closure of the ductus venosus, whereas AHR signaling in hepatocytes is necessary to generate adaptive and toxic responses of the liver in response to dioxin exposure. Taken together, these data illustrate the importance of cell-specific receptor signaling for the generation of distinct AHR-dependent physiological outcomes.

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