Linked Life Data

20237132

Source:http://linkedlifedata.com/resource/pubmed/id/20237132

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-5-21
pubmed:abstractText
It is known that a hypoxic environment is critical for trophoblast migration and invasion and is fundamental for appropriate placental perfusion. Because cysteine-rich 61 (CYR61, CCN1) and nephroblastoma overexpressed (NOV, CCN3) are expressed in the extravillous trophoblast and expression levels are deregulated in preeclampsia, we investigated their regulation properties in first-trimester placental explants and in JEG3 choriocarcinoma cells upon a physiological low oxygen tension of 1-3%. In placental explants, both proteins were expressed in the extravillous trophoblast cells and were increased upon hypoxia. JEG3 cells revealed a significant up-regulation of CYR61 and NOV intracellular as well as secreted protein upon hypoxic treatment accompanied by the stabilization of the hypoxia-inducible factor-1alpha (HIF-1alpha). Treatment with dimethyloxalylglycine to mimic hypoxia and silencing of HIF-1alpha using small interfering RNA revealed that only the increase in intracellular protein expression seems to be dependent on HIF-1alpha but obviously not the secretion process. Moreover, recombinant TGF-beta3 was able to further enhance the amount of intracellular CCN proteins as well as secreted CYR61 levels under hypoxia. These results indicate that low oxygen levels trigger elevation of intracellular as well as secreted CYR61 and NOV protein probably in two independent pathways. Addition of recombinant CYR61 and NOV proteins increases migration as well as invasion properties of JEG3 trophoblast cells, which strengthen their role in supporting trophoblast migration invasion properties. In summary, CYR61 and NOV are regulated by HIF-1alpha and TGF-beta3 in the trophoblast cell line JEG3, and their enhanced secretion could be implicated in appropriate placental invasion.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1945-7170
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
151
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2835-45
pubmed:meshHeading
pubmed-meshheading:20237132-Amino Acids, Dicarboxylic, pubmed-meshheading:20237132-Cell Hypoxia, pubmed-meshheading:20237132-Cell Line, pubmed-meshheading:20237132-Cell Movement, pubmed-meshheading:20237132-Cysteine-Rich Protein 61, pubmed-meshheading:20237132-Female, pubmed-meshheading:20237132-Humans, pubmed-meshheading:20237132-Hypoxia-Inducible Factor 1, alpha Subunit, pubmed-meshheading:20237132-Immunoblotting, pubmed-meshheading:20237132-Immunohistochemistry, pubmed-meshheading:20237132-Nephroblastoma Overexpressed Protein, pubmed-meshheading:20237132-Placenta, pubmed-meshheading:20237132-Polymerase Chain Reaction, pubmed-meshheading:20237132-Pregnancy, pubmed-meshheading:20237132-Pregnancy Trimester, First, pubmed-meshheading:20237132-Protein Stability, pubmed-meshheading:20237132-Transforming Growth Factor beta3, pubmed-meshheading:20237132-Trophoblasts
pubmed:year
2010
pubmed:articleTitle
Regulation of the matricellular proteins CYR61 (CCN1) and NOV (CCN3) by hypoxia-inducible factor-1{alpha} and transforming-growth factor-{beta}3 in the human trophoblast.
pubmed:affiliation
Department of Molecular Biology, University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't