Source:http://linkedlifedata.com/resource/pubmed/id/19443607
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
2009-7-28
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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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 beta,
http://linkedlifedata.com/resource/pubmed/chemical/kalinin,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1944-9917
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1264-71
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pubmed:dateRevised |
2011-11-2
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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
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pubmed:year |
2009
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pubmed:articleTitle |
Signaling pathways implicated in the stimulation of beta-cell proliferation by extracellular matrix.
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pubmed:affiliation |
Department of Genetic Medicine and Development, University of Geneva University Medical Center, Geneva, Switzerland. geraldine.parnaud@.unige.ch
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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