Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2000-3-3
pubmed:abstractText
Heparin-binding EGF-like growth factor (HB-EGF) is expressed in the mouse endometrial epithelium during implantation exclusively at sites apposed to embryos and accelerates the development of cultured blastocysts, suggesting that it may regulate peri-implantation development in utero. We have examined the influence of HB-EGF on mouse trophoblast differentiation in vitro and the associated intracellular signaling pathways. HB-EGF both induced intracellular Ca2+ signaling and accelerated trophoblast development to an adhesion-competent stage, but only late on gestation day 4 after ErbB4, a receptor for HB-EGF, translocated from the cytoplasm to the apical surface of trophoblast cells. The acceleration of blastocyst differentiation by HB-EGF was attenuated after inhibition of protein tyrosine kinase activity or removal of surface heparan sulfate, as expected. Chelation of intracellular Ca2+ blocked the ability of HB-EGF to accelerate development, as did inhibitors of protein kinase C or calmodulin. The absence of any effect by a phospholipase C inhibitor and the requirement for extracellular Ca2+ suggested that the accrued free cytoplasmic Ca2+ did not originate from inositol phosphate-sensitive intracellular stores, but through Ca2+ influx. Indeed, N-type Ca2+ channel blockers specifically inhibited the ability of HB-EGF to both induce Ca2+ signaling and accelerate trophoblast development. We conclude that HB-EGF accelerates the differentiation of trophoblast cells to an adhesion-competent stage by inducing Ca2+ influx, which activates calmodulin and protein kinase C. An upstream role for ErbB4 in this pathway is implicated by the timing of its translocation to the trophoblast surface.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0950-1991
pubmed:author
pubmed:issnType
Print
pubmed:volume
127
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
33-44
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:10654598-Animals, pubmed-meshheading:10654598-Biological Transport, pubmed-meshheading:10654598-Blastocyst, pubmed-meshheading:10654598-Calcium, pubmed-meshheading:10654598-Calcium Channels, pubmed-meshheading:10654598-Calcium Signaling, pubmed-meshheading:10654598-Cell Differentiation, pubmed-meshheading:10654598-Epidermal Growth Factor, pubmed-meshheading:10654598-Female, pubmed-meshheading:10654598-Heparin, pubmed-meshheading:10654598-Heparitin Sulfate, pubmed-meshheading:10654598-Humans, pubmed-meshheading:10654598-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:10654598-Male, pubmed-meshheading:10654598-Mice, pubmed-meshheading:10654598-Mice, Inbred C57BL, pubmed-meshheading:10654598-Protein Kinase C, pubmed-meshheading:10654598-Receptor, Epidermal Growth Factor, pubmed-meshheading:10654598-Trophoblasts
pubmed:year
2000
pubmed:articleTitle
Acceleration of trophoblast differentiation by heparin-binding EGF-like growth factor is dependent on the stage-specific activation of calcium influx by ErbB receptors in developing mouse blastocysts.
pubmed:affiliation
C.S. Mott Center for Human Growth and Development, Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't