Linked Life Data

15562441

Source:http://linkedlifedata.com/resource/pubmed/id/15562441

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2004-11-30
pubmed:abstractText
A network of liver-enriched transcription factors controls differentiation and morphogenesis of the liver. These factors interact via direct, feedback, and autoregulatory loops. Previous work has suggested that hepatocyte nuclear factor (HNF)-6/OC-1 and HNF-3alpha/FoxA1 participate coordinately in this hepatic network. We investigated how HNF-6 controls the expression of Foxa1. We observed that Foxa1 expression was upregulated in the liver of Hnf6(-/-) mouse embryos and in bipotential mouse embryonic liver (BMEL) cell lines derived from embryonic Hnf6(-/-) liver, suggesting that HNF-6 inhibits the expression of Foxa1. Because no evidence for a direct repression of Foxa1 by HNF-6 was found, we postulated the existence of an indirect mechanism. We found that the expression of a mediator and targets of the transforming growth factor beta (TGF-beta) signaling was increased both in Hnf6(-/-) liver and in Hnf6(-/-) BMEL cell lines. Using these cell lines, we demonstrated that TGF-beta signaling was increased in the absence of HNF-6, and that this resulted from upregulation of TGF-beta receptor II expression. We also found that TGF-beta can stimulate the expression of Foxa1 in Hnf6(+/+) cells and that inhibition of TGF-beta signaling in Hnf6(-/-) cells down-regulates the expression of Foxa1. In conclusion, we propose that Foxa1 upregulation in the absence of HNF-6 results from increased TGF-beta signaling via increased expression of the TGF-beta receptor II. We further conclude that HNF-6 inhibits Foxa1 by inhibiting the activity of the TGF-beta signaling pathway. This identifies a new mechanism of interaction between liver-enriched transcription factors whereby one factor indirectly controls another by modulating the activity of a signaling pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0270-9139
pubmed:author
pubmed:issnType
Print
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1266-74
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Transcription factor HNF-6/OC-1 inhibits the stimulation of the HNF-3alpha/Foxa1 gene by TGF-beta in mouse liver.
pubmed:affiliation
Hormone and Metabolic Research Unit, Institute of Cellular Pathology and Université Catholique de Louvain, Brussels, Belgium.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't