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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2007-11-7
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pubmed:abstractText |
Data providing direct evidence for a causative link between endothelial dysfunction, microvascular disease and diabetic end-organ damage are scarce. Here we show that activated protein C (APC) formation, which is regulated by endothelial thrombomodulin, is reduced in diabetic mice and causally linked to nephropathy. Thrombomodulin-dependent APC formation mediates cytoprotection in diabetic nephropathy by inhibiting glomerular apoptosis. APC prevents glucose-induced apoptosis in endothelial cells and podocytes, the cellular components of the glomerular filtration barrier. APC modulates the mitochondrial apoptosis pathway via the protease-activated receptor PAR-1 and the endothelial protein C receptor EPCR in glucose-stressed cells. These experiments establish a new pathway, in which hyperglycemia impairs endothelial thrombomodulin-dependent APC formation. Loss of thrombomodulin-dependent APC formation interrupts cross-talk between the vascular compartment and podocytes, causing glomerular apoptosis and diabetic nephropathy. Conversely, maintaining high APC levels during long-term diabetes protects against diabetic nephropathy.
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pubmed:commentsCorrections |
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1078-8956
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pubmed:author |
pubmed-author:BergDavid TDT,
pubmed-author:BierhausAngelikaA,
pubmed-author:BlautzikJanuschJ,
pubmed-author:BlessingErwinE,
pubmed-author:ChavakisTriantafyllosT,
pubmed-author:CoratMarcus A FMA,
pubmed-author:DeM NMN,
pubmed-author:EsmonCharles TCT,
pubmed-author:GerlitzBruceB,
pubmed-author:GrinnellBrian WBW,
pubmed-author:HerzogStefanieS,
pubmed-author:IsermannBerendB,
pubmed-author:KashifMuhammedM,
pubmed-author:MadhusudhanThatiT,
pubmed-author:NawrothPeter PPP,
pubmed-author:VinnikovIlya AIA,
pubmed-author:WeilerHartmutH,
pubmed-author:ZeierMartinM
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pubmed:issnType |
Print
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1349-58
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pubmed:meshHeading |
pubmed-meshheading:17982464-Amino Acid Substitution,
pubmed-meshheading:17982464-Animals,
pubmed-meshheading:17982464-Apoptosis,
pubmed-meshheading:17982464-Cell Line, Transformed,
pubmed-meshheading:17982464-Cells, Cultured,
pubmed-meshheading:17982464-Cytoprotection,
pubmed-meshheading:17982464-Diabetes Mellitus, Experimental,
pubmed-meshheading:17982464-Diabetic Nephropathies,
pubmed-meshheading:17982464-Endothelium, Vascular,
pubmed-meshheading:17982464-Enzyme Activation,
pubmed-meshheading:17982464-Humans,
pubmed-meshheading:17982464-Kidney Glomerulus,
pubmed-meshheading:17982464-Mice,
pubmed-meshheading:17982464-Mice, Inbred C57BL,
pubmed-meshheading:17982464-Mice, Mutant Strains,
pubmed-meshheading:17982464-Mice, Transgenic,
pubmed-meshheading:17982464-Microcirculation,
pubmed-meshheading:17982464-Podocytes,
pubmed-meshheading:17982464-Protein C,
pubmed-meshheading:17982464-Signal Transduction,
pubmed-meshheading:17982464-Thrombomodulin
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pubmed:year |
2007
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pubmed:articleTitle |
Activated protein C protects against diabetic nephropathy by inhibiting endothelial and podocyte apoptosis.
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pubmed:affiliation |
Department of Medicine I and Clinical Chemistry, University of Heidelberg, INF 410, 69120 Heidelberg, Germany. berend.isermann@med.uni-heidelberg.de
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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