Linked Life Data

9348193

Source:http://linkedlifedata.com/resource/pubmed/id/9348193

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1997-11-24
pubmed:abstractText
Transforming growth factor-beta (TGFbeta) plays an important role in bone development and remodeling. TGFbeta stimulates PGE2 production, enhances interleukin-1-stimulated PGE2 production, and can stimulate PG-mediated bone resorption. We found that TGFbeta induced prostaglandin G/H synthase (PGHS-2) messenger RNA (mRNA) and PGE2 production in neonatal mouse calvarial cultures and in primary cells derived from these calvariae. We used MC3T3-E1 cells, an immortalized osteoblastic cell line derived from mouse calvariae, to examine the mechanism of PGHS-2 induction. PGHS-2 mRNA was rapidly induced by TGFbeta (10 ng/ml) in MC3T3-E1 cells; mRNA levels peaked at 4-8 h and were still elevated at 24 h. Induction of PGHS-2 protein and PGE2 production correlated with PGHS-2 mRNA levels. In contrast, TGFbeta had much less effect on PGHS-1 mRNA levels. Unlike the response to other agonists, PGHS-2 mRNA induction by TGFbeta was not enhanced by cycloheximide pretreatment, suggesting a requirement for new protein synthesis. To study transcriptional regulation, cells were stably transfected with a PGHS-2 promoter-luciferase reporter construct containing 371 bp of the 5'-flanking region and 70 bp of untranslated DNA from the PGHS-2 gene. TGFbeta-stimulated luciferase activity paralleled PGHS-2 mRNA induction. Stimulation of luciferase activity and PGHS-2 mRNA levels by other agonists, including interleukin-1, TGF alpha, forskolin, and phorbol 13-myristate 12-acetate, were enhanced by TGFbeta. A 90% drop in luciferase activity occurred with deletion of the region from -371 to -213 bp of the PGHS-2 promoter. The PG response to TGFbeta in MC3T3-E1 cells appears to be mediated primarily by transcriptional regulation of PGHS-2 expression through one or more cis-acting elements located between -371 and -213 bp in the 5'-flanking region of the PGHS-2 gene.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
138
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4672-82
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9348193-Animals, pubmed-meshheading:9348193-Cell Line, pubmed-meshheading:9348193-Chromosome Mapping, pubmed-meshheading:9348193-Cycloheximide, pubmed-meshheading:9348193-Cyclooxygenase 2, pubmed-meshheading:9348193-Dinoprostone, pubmed-meshheading:9348193-Gene Amplification, pubmed-meshheading:9348193-Humans, pubmed-meshheading:9348193-Interleukin-1, pubmed-meshheading:9348193-Isoenzymes, pubmed-meshheading:9348193-Membrane Proteins, pubmed-meshheading:9348193-Mice, pubmed-meshheading:9348193-Mice, Inbred Strains, pubmed-meshheading:9348193-Osteoblasts, pubmed-meshheading:9348193-Phenotype, pubmed-meshheading:9348193-Promoter Regions, Genetic, pubmed-meshheading:9348193-Prostaglandin-Endoperoxide Synthases, pubmed-meshheading:9348193-RNA, Messenger, pubmed-meshheading:9348193-Recombinant Proteins, pubmed-meshheading:9348193-Transforming Growth Factor beta
pubmed:year
1997
pubmed:articleTitle
Transforming growth factor-beta1 regulation of prostaglandin G/H synthase-2 expression in osteoblastic MC3T3-E1 cells.
pubmed:affiliation
Department of Medicine, University of Connecticut Health Center, Farmington 06030, USA. pilbeam@nso.uchc.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.