Source:http://linkedlifedata.com/resource/pubmed/id/15113752
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2004-8-6
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| pubmed:abstractText |
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) are ligand-activated transcription factors that regulate cell growth, inflammation, lipid metabolism, and insulin sensitivity. PPAR-gamma in the human kidney has been described. However, the role of PPAR-gamma in proximal tubular cells with respect to cell growth and inflammation in diabetic nephropathy is largely unknown. We evaluated the effect of high (30 mM) D-glucose, thiazolidinedione pioglitazone (10 microM), and the selective PPAR-gamma agonist L-805645 (8 microM) on PPAR-gamma expression, growth, and inflammatory parameters in the proximal tubular model of HK-2 cells. PPAR-gamma was present in HK-2 cells and upregulated with 30 mM D-glucose to 177 +/- 31.2% of control (P < 0.05). PPAR-gamma activation was induced by pioglitazone to a similar level to that observed by exposure to high glucose but maximally induced by the selective agonist L-805645. However, L-805645 reduced cell viability in both 5 and 30 mM d-glucose to 73.8 +/- 3.1 and 77.6 +/- 1.4% of control (both P < 0.0001). In parallel, thymidine incorporation was reduced with L-805645 in both 5 and 30 mM D-glucose to 33.3 +/- 3.4 and 37.9 +/- 2.2%, respectively (both P < 0.0001). Flow cytometry demonstrated increased apoptosis and G(1) phase arrest in association with an increase in p21(cip1/waf1) in cells exposed to L-805645. Exposure to 30 mM D-glucose did not significantly change AP-1 promoter activity (89.0 +/- 5.5% of control); however, the addition of L-805645 significantly reduced it to 62.2 +/- 2.7% of control (P < 0.0001). Thirty nanomolar D-glucose induced transforming growth factor-beta(1) to 137.7 +/- 16.9% of control (P < 0.05), and L-805645 was able to suppress this to 68.7 +/- 5.7% of control (P < 0.01 vs. d-glucose). Exposure to 30 mM D-glucose reduced monocyte chemoattractant protein 1 levels to 78.6 +/- 7.1% (P < 0.05) of control, with the reduction more marked in the presence of either pioglitazone (P < 0.01) or L-805645 (P < 0.01). In summary, high glucose upregulates PPAR-gamma and when significantly induced demonstrates anti-proliferative and anti-inflammatory effects.
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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/CDKN1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL2,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoglycemic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/TGFB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazolidinediones,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidine,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1,
http://linkedlifedata.com/resource/pubmed/chemical/Tritium,
http://linkedlifedata.com/resource/pubmed/chemical/pioglitazone
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
1931-857X
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
287
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
F528-34
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| pubmed:dateRevised |
2011-4-28
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| pubmed:meshHeading |
pubmed-meshheading:15113752-Cell Line,
pubmed-meshheading:15113752-Cell Survival,
pubmed-meshheading:15113752-Chemokine CCL2,
pubmed-meshheading:15113752-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:15113752-Cyclins,
pubmed-meshheading:15113752-Diabetic Nephropathies,
pubmed-meshheading:15113752-Flow Cytometry,
pubmed-meshheading:15113752-Glucose,
pubmed-meshheading:15113752-Humans,
pubmed-meshheading:15113752-Hypoglycemic Agents,
pubmed-meshheading:15113752-Kidney Tubules, Proximal,
pubmed-meshheading:15113752-Promoter Regions, Genetic,
pubmed-meshheading:15113752-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:15113752-Thiazolidinediones,
pubmed-meshheading:15113752-Thymidine,
pubmed-meshheading:15113752-Transcription Factor AP-1,
pubmed-meshheading:15113752-Transcription Factors,
pubmed-meshheading:15113752-Transforming Growth Factor beta,
pubmed-meshheading:15113752-Transforming Growth Factor beta1,
pubmed-meshheading:15113752-Tritium
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| pubmed:year |
2004
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| pubmed:articleTitle |
The effect of high glucose and PPAR-gamma agonists on PPAR-gamma expression and function in HK-2 cells.
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| pubmed:affiliation |
Department of Medicine, The University of Sydney, Renal Research Group, Kolling Institute of Medical Research, Royal North Shore Hospital, New South Wales 2065, Australia.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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