Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2006-7-26
pubmed:databankReference
pubmed:abstractText
Human mesenchymal stem cells (hMSCs) exhibit the potential to contribute to a wide variety of endogenous organ tissue repair. However, the signals governing hMSC mobilization out of the bone marrow, release into the bloodstream, and migration/invasion into the target tissue are largely unknown. Since canonical Wnt signaling regulates not only tumor but also various stem cell attributes, we hypothesized that this signal transduction pathway might also be involved in governing the transmigration of hMSCs through human extracellular matrix (ECM). Stimulation of hMSCs with recombinant Wnt3a or LiCl resulted in the accumulation of the transcriptional activator beta-catenin, its translocation into the nucleus, and the upregulation of typical Wnt target genes such as cyclin D1 and membrane-type matrix metalloproteinase-1 (MT1-MMP). Moreover, both stimuli significantly enhanced hMSC proliferation up to 40%. In addition, an increase of more than twofold in the ability of hMSCs to transmigrate through Transwell filters coated with human ECM was observed. In a reverse approach, Wnt signaling in hMSCs was inhibited by knocking down the expression of either beta-catenin or low-density lipoprotein receptor-related protein 5 using RNA interference technology. These inhibition strategies resulted in downregulation of the Wnt target genes cyclin D1 and MT1-MMP, in a reduced proliferation rate, and in a strikingly diminished invasion capacity (64% and 52%). Taken together, this study provides for the first time decisive evidence that canonical Wnt signaling is critically involved in the regulation of the proliferation, as well as of the migration/invasion capacity of hMSCs, representing essential stem cell features indispensable during tissue regeneration processes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D, http://linkedlifedata.com/resource/pubmed/chemical/Cyclins, http://linkedlifedata.com/resource/pubmed/chemical/LDL-Receptor Related Proteins, http://linkedlifedata.com/resource/pubmed/chemical/LRP5 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Lithium Chloride, http://linkedlifedata.com/resource/pubmed/chemical/Low Density Lipoprotein..., http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 14, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/WNT3A protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Wnt3 Protein, http://linkedlifedata.com/resource/pubmed/chemical/Wnt3A Protein, http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1066-5099
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1892-903
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:16690780-Cell Movement, pubmed-meshheading:16690780-Cell Proliferation, pubmed-meshheading:16690780-Cells, Cultured, pubmed-meshheading:16690780-Cyclin D, pubmed-meshheading:16690780-Cyclins, pubmed-meshheading:16690780-Humans, pubmed-meshheading:16690780-LDL-Receptor Related Proteins, pubmed-meshheading:16690780-Lithium Chloride, pubmed-meshheading:16690780-Low Density Lipoprotein Receptor-Related Protein-5, pubmed-meshheading:16690780-Matrix Metalloproteinase 14, pubmed-meshheading:16690780-Mesenchymal Stem Cells, pubmed-meshheading:16690780-Molecular Sequence Data, pubmed-meshheading:16690780-RNA Interference, pubmed-meshheading:16690780-Recombinant Proteins, pubmed-meshheading:16690780-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16690780-Signal Transduction, pubmed-meshheading:16690780-Wnt Proteins, pubmed-meshheading:16690780-Wnt3 Protein, pubmed-meshheading:16690780-Wnt3A Protein, pubmed-meshheading:16690780-beta Catenin
pubmed:year
2006
pubmed:articleTitle
Wnt signaling regulates the invasion capacity of human mesenchymal stem cells.
pubmed:affiliation
Department of Surgery, Division of Clinical Chemistry and Clinical Biochemistry, Ludwig-Maximilians-University, Munich, Germany. Peter.Neth@med.uni-muenchen.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't