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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-8-31
pubmed:abstractText
The aryl hydrocarbon receptor (AHR) is believed to mediate many of the toxic, carcinogenic, and teratogenic effects of environmental contaminants such as dioxins, polycyclic aromatic hydrocarbons, and polyhalogenated biphenyls. Ligands for the AHR have been shown to influence cell proliferation, differentiation, and apoptosis, but the mechanism by which the AHR affects the cell cycle is not known. Increased levels of mature transforming growth factor-beta (TGFbeta) has been correlated with reduced cell proliferation and increased rates of apoptosis and fibrosis. Based on the increase in portal fibrosis and small liver size observed in AHR-null (Ahr-/-) mice, the relationship between TGFbeta expression and apoptosis in this mouse line was analyzed. Livers from Ahr-/- mice had marked increase in active TGFbeta1 and TGFbeta3 proteins and elevated numbers of hepatocytes undergoing apoptosis compared with wild-type mice. Furthermore, increases in TGFbeta and apoptotic cells were found in the portal areas of the liver, where fibrosis is found in the Ahr-/- mice. In vitro, primary hepatocyte cultures from Ahr-/- mice exhibited a high number of cells in later stages of apoptosis and an elevated secretion of active TGFbeta into the media compared with cultures from wild-type mice, which have previously been shown to secrete only latent forms of the molecule. Conditioned media from Ahr-/- hepatocytes stimulated apoptosis in cultured hepatocytes from wild-type mice. Taken together, these findings suggest that the phenotypic abnormalities in Ahr-/- mice could be mediated in part by abnormal levels of active TGFbeta and altered cell cycle control.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
313-21
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
The involvement of aryl hydrocarbon receptor in the activation of transforming growth factor-beta and apoptosis.
pubmed:affiliation
Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
pubmed:publicationType
Journal Article