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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2003-12-3
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pubmed:abstractText |
Chronic elevated glucose levels and activation of the renal renin-angiotensin system have been implicated in the pathogenesis of diabetic nephropathy. We tested the ability of lisofylline (LSF), a novel antiinflammatory compound, to prevent extracellular matrix (ECM) accumulation and growth factor production by human mesangial cells (HMCs) cultured in chronic elevated glucose (HG) or angiotensin II (AngII). HMCs were cultured in normal glucose (NG) (5.5 mm) and in HG (25 mm) for 7 d or with 10-7 m AngII for 4 h with or without LSF. Levels of the ECM protein fibronectin and TGF-beta in media were shown to increase in HG compared with NG. LSF decreased HG-induced fibronectin and TGF-beta production to control levels. Increased expression of collagen type IV and laminin was observed in AngII-cultured HMCs. LSF protected HMCs from the AngII induction of these key matrix proteins. cAMP-responsive binding element phosphorylation was significantly higher in both HG and AngII-cultured HMCs. LSF reduced phosphorylation of both cAMP-responsive binding element and p38 MAPK compared with control. These data demonstrate that LSF protects HMCs from HG- and AngII-mediated ECM deposition by the reduction of matrix protein secretion possibly through regulation of TGF-beta production and modulation of the p38 MAPK pathway. These results suggest that LSF may provide therapeutic benefit for prevention or treatment of diabetic nephropathy.
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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 |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin II,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/CTGF protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Connective Tissue Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response...,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Matrix Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fibronectins,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Pentoxifylline,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Vasoconstrictor Agents,
http://linkedlifedata.com/resource/pubmed/chemical/lisofylline,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0013-7227
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
144
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5227-31
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12960000-Angiotensin II,
pubmed-meshheading:12960000-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:12960000-Cells, Cultured,
pubmed-meshheading:12960000-Connective Tissue Growth Factor,
pubmed-meshheading:12960000-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:12960000-Extracellular Matrix,
pubmed-meshheading:12960000-Extracellular Matrix Proteins,
pubmed-meshheading:12960000-Fibronectins,
pubmed-meshheading:12960000-Gene Expression,
pubmed-meshheading:12960000-Glomerular Mesangium,
pubmed-meshheading:12960000-Glucose,
pubmed-meshheading:12960000-Humans,
pubmed-meshheading:12960000-Hyperglycemia,
pubmed-meshheading:12960000-Immediate-Early Proteins,
pubmed-meshheading:12960000-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:12960000-MAP Kinase Signaling System,
pubmed-meshheading:12960000-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12960000-Pentoxifylline,
pubmed-meshheading:12960000-Phosphorylation,
pubmed-meshheading:12960000-Transforming Growth Factor beta,
pubmed-meshheading:12960000-Vasoconstrictor Agents,
pubmed-meshheading:12960000-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2003
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pubmed:articleTitle |
Lisofylline, a novel antiinflammatory compound, protects mesangial cells from hyperglycemia- and angiotensin II-mediated extracellular matrix deposition.
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pubmed:affiliation |
Division of Endocrinology and Metabolism, University of Virginia Medical Center, Charlottesville, Virginia 22908-1405, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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