Linked Life Data

21256838

Source:http://linkedlifedata.com/resource/pubmed/id/21256838

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-3-7
pubmed:abstractText
Wnt4 and ?-catenin are both required for nephrogenesis, but studies using TCF-reporter mice suggest that canonical Wnt signaling is not activated in metanephric mesenchyme (MM) during its conversion to the epithelia of the nephron. To better define the role of Wnt signaling, we treated rat metanephric mesenchymal progenitors directly with recombinant Wnt proteins. These studies revealed that Wnt4 protein, which is required for nephron formation, induces tubule formation and differentiation markers Lim1 and E-cadherin in MM cells, but does not activate a TCF reporter or up regulate expression of canonical Wnt target gene Axin-2 and has little effect on the stabilization of ?-catenin or phosphorylation of disheveled-2. Furthermore, Wnt4 causes membrane localization of ZO-1 and occludin in tight junctions. To directly examine the role of ?-catenin/TCF-dependent transcription, we developed synthetic cell-permeable analogs of ?-catenin's helix C, which is required for transcriptional activation, in efforts to specifically inhibit canonical Wnt signaling. One inhibitor blocked TCF-dependent transcription and induced degradation of ?-catenin but did not affect tubule formation and stimulated the expression of Lim1 and E-cadherin. Since a canonical mechanism appears not to be operative in tubule formation, we assessed the involvement of the non-canonical Ca(2+)-dependent pathway. Treatment of MM cells with Wnt4 induced an influx of Ca(2+) and caused phosphorylation of CaMKII. Moreover, Ionomycin, a Ca(2+)-dependent pathway activator, stimulated tubule formation. These results demonstrate that the canonical Wnt pathway is not responsible for mesenchymal-epithelial transition (MET) in nephron formation and suggest that the non-canonical calcium/Wnt pathway mediates Wnt4-induced tubulogenesis in the kidney.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1095-564X
pubmed:author
pubmed:copyrightInfo
Published by Elsevier Inc.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
352
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
58-69
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:21256838-Animals, pubmed-meshheading:21256838-Calcium Signaling, pubmed-meshheading:21256838-Calcium-Calmodulin-Dependent Protein Kinase Type 2, pubmed-meshheading:21256838-Cell Differentiation, pubmed-meshheading:21256838-Cells, Cultured, pubmed-meshheading:21256838-Enzyme Activation, pubmed-meshheading:21256838-Gene Expression Regulation, Developmental, pubmed-meshheading:21256838-Genes, Reporter, pubmed-meshheading:21256838-Humans, pubmed-meshheading:21256838-Ionomycin, pubmed-meshheading:21256838-Kidney Tubules, pubmed-meshheading:21256838-Mesoderm, pubmed-meshheading:21256838-Mice, pubmed-meshheading:21256838-Models, Biological, pubmed-meshheading:21256838-Morphogenesis, pubmed-meshheading:21256838-Nephrons, pubmed-meshheading:21256838-Rats, pubmed-meshheading:21256838-Signal Transduction, pubmed-meshheading:21256838-TCF Transcription Factors, pubmed-meshheading:21256838-Transcription, Genetic, pubmed-meshheading:21256838-Transcriptional Activation, pubmed-meshheading:21256838-Wnt Proteins, pubmed-meshheading:21256838-Wnt4 Protein, pubmed-meshheading:21256838-beta Catenin
pubmed:year
2011
pubmed:articleTitle
Wnt4 induces nephronic tubules in metanephric mesenchyme by a non-canonical mechanism.
pubmed:affiliation
Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural