Linked Life Data

19635564

Source:http://linkedlifedata.com/resource/pubmed/id/19635564

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-2-3
pubmed:abstractText
Renin-angiotensin system (RAS) plays a central role in the development and progression of diabetic nephropathy. Further, there is a growing body of evidence that advanced glycation end products (AGEs) and their receptor (RAGE) axis also contributes to diabetic nephropathy. However, the pathophysiological crosstalk between the RAS and AGE-RAGE system in tubular cell injury, which is more important than glomerulopathy in terms of renal prognosis in diabetic nephropathy, remains unknown. In this study, we examined whether and how irbesartan, an angiotensin II type 1 receptor blocker (ARB), inhibited the AGE-induced tubular cell apotptosis and damage in vitro. Gene expression was analyzed by quantitative real-time reverse transcription-polymerase chain reactions. Intracellular formation of reactive oxygen species (ROS) was measured with dihydroethidium staining. Apoptosis levels were evaluated for DNA fragments with an enzyme-linked immunosorbent assay kit and for caspase-3 activity. Irbesartan inhibited the AGE-induced up-regulation of RAGE mRNA levels and subsequently reduced ROS generation in human proximal tubular cells. AGEs induced apoptosis and increased inflammatory, thrombogenic and fibrogenic gene expressions in tubular cells, which were also blocked by the treatment with irbesartan. Our present data suggest that there exists a crosstalk between the RAS and AGE-RAGE system in tubular cell apoptosis and damage. Blockade of the RAS by irbesartan may play a protective role against tubular injury in diabetes by attenuating the deleterious effects of AGEs via down-regulation of RAGE.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin II Type 1 Receptor..., http://linkedlifedata.com/resource/pubmed/chemical/Biphenyl Compounds, http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3, http://linkedlifedata.com/resource/pubmed/chemical/Glycosylation End Products, Advanced, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic, http://linkedlifedata.com/resource/pubmed/chemical/Serum Albumin, Bovine, http://linkedlifedata.com/resource/pubmed/chemical/Tetrazoles, http://linkedlifedata.com/resource/pubmed/chemical/advanced glycation end..., http://linkedlifedata.com/resource/pubmed/chemical/advanced glycosylation end-product..., http://linkedlifedata.com/resource/pubmed/chemical/irbesartan
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1096-1186
pubmed:author
pubmed:copyrightInfo
Copyright 2009 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
34-9
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Irbesartan inhibits advanced glycation end product (AGE)-induced proximal tubular cell injury in vitro by suppressing receptor for AGEs (RAGE) expression.
pubmed:affiliation
Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume 830-0011, Fukuoka, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't