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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0037083,
umls-concept:C0040648,
umls-concept:C0044602,
umls-concept:C0079904,
umls-concept:C0081714,
umls-concept:C0085828,
umls-concept:C0185117,
umls-concept:C0205263,
umls-concept:C0225828,
umls-concept:C0285761,
umls-concept:C0383327,
umls-concept:C0439064,
umls-concept:C1150481,
umls-concept:C1150571,
umls-concept:C1150587,
umls-concept:C1367731,
umls-concept:C1368105,
umls-concept:C1412828,
umls-concept:C1451005,
umls-concept:C1515877,
umls-concept:C1705325,
umls-concept:C1705632,
umls-concept:C1710082,
umls-concept:C1879547,
umls-concept:C2911684
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pubmed:issue |
4
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pubmed:dateCreated |
2010-8-31
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pubmed:abstractText |
The transmembrane glycoprotein extracellular matrix metalloproteinase inducer (EMMPRIN), and the pleiotropic proinflammatory cytokine interleukin (IL)-18, play critical roles in myocardial remodeling, by inducing matrix degrading metalloproteinases (MMPs). Previously we showed that IL-18 induces EMMPRIN expression in cardiomyocytes via MyD88/IRAK4/TRAF6/JNK-dependent Sp1 activation. Here in reciprocal studies we demonstrate that EMMPRIN is a potent inducer of IL-18 transcription, protein expression and protein secretion in primary mouse cardiomyocytes. We show for the first time that EMMPRIN stimulates the activation of NF-kappaB, AP-1, CREB, and ATF-2 in cardiomyocytes, and induces IL-18 expression via Rac1-dependent PI3K/Akt/IKK/NF-kappaB and MKK7/JNK/AP-1 signaling. Moreover, EMMPRIN induces robust time-dependent induction of various MMP mRNAs. EMMPRIN also induces the mRNA of TIMPs 1 and 3, but in a delayed fashion. These results suggest that IL-18-induced EMMPRIN expression may favor net MMP expression and ECM destruction, and thus identify both as potential therapeutic targets in countering adverse myocardial remodeling.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD147,
http://linkedlifedata.com/resource/pubmed/chemical/Bsg protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-18,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 7,
http://linkedlifedata.com/resource/pubmed/chemical/Map2k7 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Neuropeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Rac1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/rac GTP-Binding Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1095-8584
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2010 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:volume |
49
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
655-63
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pubmed:dateRevised |
2011-10-3
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pubmed:meshHeading |
pubmed-meshheading:20538003-Animals,
pubmed-meshheading:20538003-Antigens, CD147,
pubmed-meshheading:20538003-Cells, Cultured,
pubmed-meshheading:20538003-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:20538003-I-kappa B Kinase,
pubmed-meshheading:20538003-Interleukin-18,
pubmed-meshheading:20538003-MAP Kinase Kinase 7,
pubmed-meshheading:20538003-Male,
pubmed-meshheading:20538003-Mice,
pubmed-meshheading:20538003-Mice, Inbred C57BL,
pubmed-meshheading:20538003-Myocytes, Cardiac,
pubmed-meshheading:20538003-NF-kappa B,
pubmed-meshheading:20538003-Neuropeptides,
pubmed-meshheading:20538003-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:20538003-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:20538003-Transcription Factor AP-1,
pubmed-meshheading:20538003-rac GTP-Binding Proteins
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pubmed:year |
2010
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pubmed:articleTitle |
EMMPRIN activates multiple transcription factors in cardiomyocytes, and induces interleukin-18 expression via Rac1-dependent PI3K/Akt/IKK/NF-kappaB andMKK7/JNK/AP-1 signaling.
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pubmed:affiliation |
Research Service, Southeast Louisiana Veterans Health Care System, New Orleans, LA 70161, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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