Linked Life Data

16380460

Source:http://linkedlifedata.com/resource/pubmed/id/16380460

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-5-9
pubmed:abstractText
The microfibrillar protein fibrillin-1 is a component of the mesangial matrix. Defects in fibrillin-1 predisposes individuals to vascular damage in Marfan syndrome, but the role of fibrillin-1 in kidney disease is unknown. We hypothesized that fibrillin-1 is involved in hypertensive or diabetic glomerular disease. DOCA-salt hypertension or streptozotocin (STZ) diabetes led to a significant increase in glomerular fibrillin-1 deposition. To test the functional role of fibrillin-1, DOCA hypertension and STZ diabetes were induced in mice homozygous for a mutation leading to a fivefold lower expression of fibrillin-1 (mgR/mgR). Untreated male mgR/mgR mice usually die from aortic dissection during the first 4 mo of life. All DOCA-treated mgR/mgR mice died within 2 wk after onset of DOCA treatment. DOCA-treated heterozygous (mgR/+) and their wild-type littermates displayed similar blood pressure levels, but albuminuria was significantly lower in mgR/+ than in wild-type mice after DOCA treatment. Similarly, STZ diabetic mgR/mgR and mgR/+ developed lower albuminuria than wild-type mice despite higher blood glucose levels in mgR/mgR and mgR/+ compared with wild-type mice. Blood pressure, blood glucose, and albuminuria did not differ among untreated mgR/mgR, mgR/+, and wild-type mice, respectively. In diabetic mgR/+ and mgR/mgR, but not in wild-type mice, an induction of glomerular decorin expression was observed. Thus underexpression of fibrillin-1 predisposes individuals to lethal aortic dissection in the presence of hypertension. On the other hand, albuminuria as a parameter of microvascular damage in hypertension and diabetes was ameliorated in fibrillin-1-underexpressing mice, possibly due to a compensatory upregulation of decorin. We conclude that fibrillin-1 may contribute to glomerular damage in hypertensive and diabetic kidney disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1931-857X
pubmed:author
pubmed:issnType
Print
pubmed:volume
290
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
F1329-36
pubmed:dateRevised
2011-4-28
pubmed:meshHeading
pubmed-meshheading:16380460-Albuminuria, pubmed-meshheading:16380460-Animals, pubmed-meshheading:16380460-Decorin, pubmed-meshheading:16380460-Desoxycorticosterone, pubmed-meshheading:16380460-Diabetes Mellitus, Experimental, pubmed-meshheading:16380460-Diabetic Nephropathies, pubmed-meshheading:16380460-Extracellular Matrix Proteins, pubmed-meshheading:16380460-Female, pubmed-meshheading:16380460-Heterozygote, pubmed-meshheading:16380460-Homozygote, pubmed-meshheading:16380460-Hypertension, pubmed-meshheading:16380460-Kidney Glomerulus, pubmed-meshheading:16380460-Male, pubmed-meshheading:16380460-Mice, pubmed-meshheading:16380460-Microfilament Proteins, pubmed-meshheading:16380460-Mutation, pubmed-meshheading:16380460-Proteoglycans, pubmed-meshheading:16380460-Rats, pubmed-meshheading:16380460-Rats, Sprague-Dawley
pubmed:year
2006
pubmed:articleTitle
Role of fibrillin-1 in hypertensive and diabetic glomerular disease.
pubmed:affiliation
Hospital for Children and Adolescents, University of Erlangen-Nurnberg, Erlangen, Germany. andrea.hartner@rzmail.uni-erlangen.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't