Linked Life Data

15941850

Source:http://linkedlifedata.com/resource/pubmed/id/15941850

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2005-9-27
pubmed:abstractText
Fibrinogen is a plasma protein synthesized by the liver. It is composed of three chains (alpha, beta, gamma). In addition to its main function as a coagulation factor, this acute phase protein is also a risk marker for atherosclerosis. Retinoic acid receptor-related orphan receptor (ROR)alpha is a nuclear receptor modulating physiopathological processes such as cerebellar ataxia, inflammation, atherosclerosis, and angiogenesis. In this study, we identified RORalpha as a regulator of fibrinogen-beta gene expression in human hepatoma cells and in mouse liver. A putative RORalpha response element (RORE) was identified in the human fibrinogen-beta promoter. EMSA showed that RORalpha binds specifically to this RORE, and cotransfection experiments in HepG2 hepatoma cells indicated that this RORE confers RORalpha-dependent transcriptional activation to both the human fibrinogen-beta and the thymidine kinase promoters. Stable transfection experiments in HepG2 and Hep3B hepatoma cells demonstrated that overexpression of RORalpha specifically increases endogenous fibrinogen-beta mRNA levels. Chromatin immunoprecipitation experiments revealed that the fibrinogen-beta RORE is occupied by RORalpha in HepG2 cells. Thus, the human fibrinogen-beta gene is a direct target for RORalpha. Furthermore, fibrinogen-beta mRNA levels in liver and plasma fibrinogen concentrations are specifically decreased in staggerer mice, which are homozygous for a deletion invalidating the Rora gene. Taken together, these data add further evidence for an important role of RORalpha in the control of liver gene expression with potential pathophysiological consequences on coagulation and cardiovascular risk.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2517-26
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15941850-Animals, pubmed-meshheading:15941850-Base Sequence, pubmed-meshheading:15941850-Binding Sites, pubmed-meshheading:15941850-Cell Line, pubmed-meshheading:15941850-DNA, pubmed-meshheading:15941850-Fibrinogen, pubmed-meshheading:15941850-Genes, Reporter, pubmed-meshheading:15941850-Humans, pubmed-meshheading:15941850-Liver, pubmed-meshheading:15941850-Mice, pubmed-meshheading:15941850-Mice, Inbred C57BL, pubmed-meshheading:15941850-Mice, Neurologic Mutants, pubmed-meshheading:15941850-Nuclear Receptor Subfamily 1, Group F, Member 1, pubmed-meshheading:15941850-Promoter Regions, Genetic, pubmed-meshheading:15941850-RNA, Messenger, pubmed-meshheading:15941850-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:15941850-Recombinant Proteins, pubmed-meshheading:15941850-Trans-Activators, pubmed-meshheading:15941850-Transcriptional Activation, pubmed-meshheading:15941850-Transfection
pubmed:year
2005
pubmed:articleTitle
The gene encoding fibrinogen-beta is a target for retinoic acid receptor-related orphan receptor alpha.
pubmed:affiliation
Centre National de la Recherche Scientifique UPR9078, Faculté de Médecine René Descartes Paris 5, site Necker, 75015 Paris, France.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't