Linked Life Data

10504483

Source:http://linkedlifedata.com/resource/pubmed/id/10504483

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1999-12-2
pubmed:abstractText
Renal tubular atrophy predicts a poor prognosis in chronic renal failure, but the molecular mechanisms that regulate tubular atrophy are unknown. Because the Fas apoptosis pathway has been implicated in disease pathogenesis and Fas is expressed in kidney, we hypothesized that Fas-mediated renal tubule epithelial cell (RTC) apoptosis contributes to tubular atrophy in chronic renal failure. Immunohistochemical analyses of renal sections from two murine models of progressive renal disease revealed increases in RTC Fas expression and apoptosis compared with tissue sections from age-matched control kidneys. Increased RTC apoptosis was not accompanied by compensatory hyperplasia, suggesting that RTCs targeted for Fas-dependent apoptotic deletion contribute to tubular atrophy. These data are supported by in vitro studies that showed that interleukin-1alpha or tumor necrosis factor-alpha, cytokines that are secreted in chronic renal failure, stimulated increases in Fas expression in cultured RTCs. Both murine kidney cortex and RTCs in culture demonstrated constitutive expression of Fas ligand, a feature that is characteristically restricted to lymphocytes and immune-privileged tissues and previously unrecognized in RTCs. Functional studies revealed that interleukin-1alpha-stimulated RTC Fas expression was accompanied by increased apoptosis, which was inhibited by blocking anti-Fas ligand antibodies. The data suggest that up-regulated RTC Fas binds to Fas ligand on adjacent RTCs, which then leads to RTC death by fratricide. We propose this pathway as an initiating mechanism of tubular atrophy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0085-2538
pubmed:author
pubmed:issnType
Print
pubmed:volume
56
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1313-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Involvement of Fas-dependent apoptosis in renal tubular epithelial cell deletion in chronic renal failure.
pubmed:affiliation
MetroHealth Medical Center, Division of Nephrology, Cleveland, Ohio 44109-1998, USA. jrs15@po.cwru.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't