Linked Life Data

15155569

Source:http://linkedlifedata.com/resource/pubmed/id/15155569

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2004-8-23
pubmed:abstractText
Hypoxia occurs during the development of placenta in the first trimester and is implicated in trophoblast differentiation. Intervillous blood flow increases after 10 wk of gestation and results in exposure of trophoblast cells to oxygen. Before this time, low oxygen appears to prevent trophoblast differentiation toward an invasive phenotype. The oxygen-regulated early events of trophoblast differentiation are mediated by TGF-beta3. TGF-beta3 plays a vital role in trophoblast differentiation, and its overexpression can be found in preeclamptic placenta. We sought to determine the mechanism of TGF-beta3 expression through hypoxia-inducible factor (HIF)-1. We show that HIF-1alpha and TGF-beta3 are overexpressed in preeclamptic placenta. Hypoxia not only transactivates the TGF-beta3 promoter activity but also enhances endogenous TGF-beta3 expression. Using the TGF-beta3 promoter deletion mutants, we show that the region between -90 and -60, which contains a putative HIF-1 consensus motif, is crucial for HIF-1-mediated transactivation. Electrophoretic mobility shift assays show that HIF-1 binds to the oligonucleotide containing the HIF-1 motif. Also, introduction of an antisense oligonucleotide for HIF-1 diminishes TGF-beta3 expression during hypoxia, indicating that the up-regulation of TGF-beta3 by hypoxia is mediated through HIF-1. Our results provide evidence that regulation of TGF-beta3 promoter activity by HIF-1 represents a mechanism for trophoblast differentiation during hypoxia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
145
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4113-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Hypoxia-inducible factor-1 transactivates transforming growth factor-beta3 in trophoblast.
pubmed:affiliation
Department of Obstetrics and Gynecology, Tokyo Medical University, 6-7-1 Nishishinjuku Shinjuku, Tokyo 160-0023, Japan. nishih@tokyo-med.ac.jp.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't