Linked Life Data

21102505

Source:http://linkedlifedata.com/resource/pubmed/id/21102505

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-3-30
pubmed:abstractText
Podocyte injury has been suggested to have a pivotal role in the pathogenesis of diabetic glomerulopathy. To glean insights into molecular mechanisms underlying diabetic podocyte injury, we generated temporal global gene transcript profiles of podocytes exposed to high glucose for a time interval of 1 or 2 weeks using microarrays. A number of genes were altered at both 1 and 2 weeks of glucose exposure compared with controls grown under normal glucose. These included extracellular matrix modulators, cell cycle regulators, extracellular transduction signals and membrane transport proteins. Novel genes that were altered at both 1 and 2 weeks of high-glucose exposure included neutrophil gelatinase-associated lipocalin (LCN2 or NGAL, decreased by 3.2-fold at 1 week and by 7.2-fold at 2 weeks), endothelial lipase (EL, increased by 3.6-fold at 1 week and 3.9-fold at 2 week) and UDP-glucuronosyltransferase 8 (UGT8, increased by 3.9-fold at 1 week and 5.0-fold at 2 weeks). To further validate these results, we used real-time PCR from independent podocyte cultures, immunohistochemistry in renal biopsies and immunoblotting on urine specimens from diabetic patients. A more detailed time course revealed changes in LCN2 and EL mRNA levels as early as 6 hours and in UGT8 mRNA level at 12 hours post high-glucose exposure. EL immunohistochemistry on human tissues showed markedly increased expression in glomeruli, and immunoblotting readily detected EL in a subset of urine samples from diabetic nephropathy patients. In addition to previously implicated roles of these genes in ischemic or oxidative stress, our results further support their importance in hyperglycemic podocyte stress and possibly diabetic glomerulopathy pathogenesis and diagnosis in humans.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1530-0307
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
91
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
488-98
pubmed:dateRevised
2011-10-12
pubmed:meshHeading
pubmed-meshheading:21102505-Acute-Phase Proteins, pubmed-meshheading:21102505-Animals, pubmed-meshheading:21102505-Cell Line, Transformed, pubmed-meshheading:21102505-Diabetic Nephropathies, pubmed-meshheading:21102505-Dose-Response Relationship, Drug, pubmed-meshheading:21102505-Drug Administration Schedule, pubmed-meshheading:21102505-Ganglioside Galactosyltransferase, pubmed-meshheading:21102505-Glucose, pubmed-meshheading:21102505-Humans, pubmed-meshheading:21102505-Kidney Glomerulus, pubmed-meshheading:21102505-Lipase, pubmed-meshheading:21102505-Lipocalins, pubmed-meshheading:21102505-Mice, pubmed-meshheading:21102505-Oncogene Proteins, pubmed-meshheading:21102505-Podocytes, pubmed-meshheading:21102505-RNA, Messenger, pubmed-meshheading:21102505-Retrospective Studies, pubmed-meshheading:21102505-Time Factors, pubmed-meshheading:21102505-Tissue Array Analysis
pubmed:year
2011
pubmed:articleTitle
Expression profiles of podocytes exposed to high glucose reveal new insights into early diabetic glomerulopathy.
pubmed:affiliation
Renal Division, Department of Internal Medicine, Washington University, School of Medicine, St Louis, MO 63110, USA. SJain22@WUSTL.EDU
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural