Source:http://linkedlifedata.com/resource/pubmed/id/11304520
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2001-4-17
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pubmed:abstractText |
The mechanisms by which persistent proteinuria induces interstitial inflammation and fibrosis are not well known, although nuclear factor-kappaB (NF-kappaB), which regulates the transcription of many genes involved in renal injury, could be implicated. In rats with intense proteinuria, we studied the renal activation of NF-kappaB as well as the potential involvement of the vasoactive hormones angiotensin II (Ang II) and endothelin-1 (ET-1). Uninephrectomized Wistar-Kyoto rats receiving 1 g/d of BSA had proteinuria but no renal morphological lesions at day 1. By contrast, tubular atrophy and/or dilation and mononuclear cell infiltration were observed after 8 or 28 days of BSA administration, coinciding with maximal proteinuria. In relation to control uninephrectomized rats, the renal cortex of nephritic rats showed an increment in the activation of NF-kappaB at all time periods studied. By in situ Southwestern histochemistry, NF-kappaB activity was mainly localized in proximal tubules, interstitial mononuclear cells, and, to a lesser extent, the glomeruli. The administration of the ACE inhibitor quinapril plus the ET(A)/ET(B) receptor antagonist bosentan during 28 days to BSA-overloaded animals diminished proteinuria, renal lesions, and NF-kappaB activity more markedly than single drugs. Cultured tubular epithelial cells exposed to BSA revealed an intense NF-kappaB activation in a time- and dose-dependent manner. Incubation of cells with receptor antagonists of Ang II (AT(1): losartan and AT(2): PD-123,319) or ET-1 (ET(A): BQ123 and ET(B): IRL1038) inhibited significantly the BSA-induced NF-kappaB activity (90%, 75%, 90%, and 60% of inhibition versus basal, respectively). Our results show that overload proteinuria causes NF-kappaB activation in tubular epithelial cells both in vivo and in vitro. The vasoactive peptides Ang II and ET-1 appear to be implicated in this effect. The results reveal a novel mechanism of perpetuation of renal damage induced by persistent proteinuria.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1524-4563
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
37
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1171-8
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11304520-Analysis of Variance,
pubmed-meshheading:11304520-Angiotensin II,
pubmed-meshheading:11304520-Animals,
pubmed-meshheading:11304520-Atrophy,
pubmed-meshheading:11304520-Cell Line,
pubmed-meshheading:11304520-Endothelin-1,
pubmed-meshheading:11304520-Epithelial Cells,
pubmed-meshheading:11304520-Female,
pubmed-meshheading:11304520-Kidney Cortex,
pubmed-meshheading:11304520-Kidney Tubules,
pubmed-meshheading:11304520-NF-kappa B,
pubmed-meshheading:11304520-Nephrectomy,
pubmed-meshheading:11304520-Nephritis,
pubmed-meshheading:11304520-Proteinuria,
pubmed-meshheading:11304520-Rats,
pubmed-meshheading:11304520-Rats, Inbred WKY
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pubmed:year |
2001
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pubmed:articleTitle |
Activation of NF-kappaB in tubular epithelial cells of rats with intense proteinuria: role of angiotensin II and endothelin-1.
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pubmed:affiliation |
Renal and Vascular Research Laboratory, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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