Linked Life Data

16443768

Source:http://linkedlifedata.com/resource/pubmed/id/16443768

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-1-30
pubmed:abstractText
Many factors are involved in the pathogenesis of diabetic nephropathy. A single gene abnormality may be prerequisite but insufficient to the disease to manifest. It is therefore only when a second or sometimes a third damage is associated that the consequences of pathogenic phenotypes become evident. We generated the triple transgenic mice overexpressing megsin (a novel glomerular-specific serpin), a receptor for advanced glycation end products (RAGE), and inducible nitric oxide synthase (iNOS). Compared with the single- or two-gene transgenic mice, the triple transgenic mice developed, at an early age (16 weeks), severe albuminuria and renal damage with all of the characteristics of human diabetic nephropathy (i.e., glomerular hypertrophy, diffuse mesangial expansion, inflammatory cell infiltration, and interstitial fibrosis). Interestingly, 30-40% of glomeruli exhibit nodule-like lesions. Oxidative and carbonyl stress makers (pentosidine, N(epsilon)-carboxymethyllysine, and 8-hydroxy-deoxyguanosine) were significantly higher in the triple transgenic mice. The iNOS transgenic mice have a diabetes phenotype, the renal consequences of which are moot, and the superimposition of RAGE leads to more conspicuous manifestations. By additional overexpression of megsin, a gene known to be involved in mesangial proliferation and expansion, these local consequences become dramatically manifest and approximate those observed in human pathology. This multiple hit approach is of interest in consideration of the sequential events during development of diabetic nephropathy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
356-66
pubmed:dateRevised
2008-8-26
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
A severe diabetic nephropathy model with early development of nodule-like lesions induced by megsin overexpression in RAGE/iNOS transgenic mice.
pubmed:affiliation
Institute of Medical Sciences and Division of Nephrology, Hypertension and Metabolism, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't