Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2009-7-28
pubmed:abstractText
Laminin-5-rich extracellular matrix derived from 804G cells (804G-ECM) induces spreading, improves glucose-stimulated insulin secretion, and increases survival and proliferation of rat pancreatic beta-cells. The aim of the study was to determine growth signaling pathways activated by ECM with a particular focus on Ca(2+)-dependent transcription factors. 804G-ECM increased rat beta-cell proliferation, and this stimulation was glucose and Ca(2+) dependent. NF-kappaB nuclear translocation as well as IkappaBalpha gene expression were also Ca(2+) dependent. Inhibition of NF-kappaB almost completely blocked 804G-ECM-stimulated beta-cell proliferation as did the soluble IL-1 receptor antagonist IL-1Ra. 804G-ECM-induced proliferation was also blocked by cyclosporin A and the VIVIT peptide, suggesting involvement of nuclear factor of activated T cells (NFAT)/calcineurin. Use of selective inhibitors further implicated other pathways in this process. Inhibition of phosphatidylinositol 3-kinase and protein kinase A both prevented beta-cell replication stimulated by 804G-ECM. Conversely, inhibition of MAPK, c-Jun N-terminal kinase, p38, and glycogen synthase kinase-3beta increased beta-cell proliferation on 804G-ECM. Our results suggest that Ca(2+) entry, which is necessary for increased beta-cell proliferation on 804G-ECM, is also involved in 804G-ECM-induced NF-kappaB activity. It is proposed that increased cytosolic Ca(2+) leads to activation of the transcription factors NFAT and NF-kappaB that in turn increase beta-cell proliferation. Activation of phosphatidylinositol 3-kinase by 804G-ECM also increases proliferation possibly by synergistic coactivation of NFAT via inhibition of glycogen synthase kinase-3beta, whereas IL-1beta may amplify the process by feed-forward activation of NF-kappaB. Conversely, inhibition of the MAPK pathway increased beta-cell proliferation, indicating a counterregulatory restraining role for this signaling pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1944-9917
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1264-71
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:19443607-Animals, pubmed-meshheading:19443607-Calcium, pubmed-meshheading:19443607-Cell Adhesion Molecules, pubmed-meshheading:19443607-Cell Proliferation, pubmed-meshheading:19443607-Extracellular Matrix, pubmed-meshheading:19443607-Glycogen Synthase Kinase 3, pubmed-meshheading:19443607-Insulin-Secreting Cells, pubmed-meshheading:19443607-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:19443607-MAP Kinase Signaling System, pubmed-meshheading:19443607-Male, pubmed-meshheading:19443607-NF-kappa B, pubmed-meshheading:19443607-Phosphatidylinositol 3-Kinases, pubmed-meshheading:19443607-Rats, pubmed-meshheading:19443607-Rats, Wistar, pubmed-meshheading:19443607-Signal Transduction, pubmed-meshheading:19443607-Transcription Factors, pubmed-meshheading:19443607-p38 Mitogen-Activated Protein Kinases
pubmed:year
2009
pubmed:articleTitle
Signaling pathways implicated in the stimulation of beta-cell proliferation by extracellular matrix.
pubmed:affiliation
Department of Genetic Medicine and Development, University of Geneva University Medical Center, Geneva, Switzerland. geraldine.parnaud@.unige.ch
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't