@entity205 induced @entity137 in XXXX renal collecting duct cells: interference with enhanced hypertonicity induced apoptosis.

@entity137 @entity870 @entity26 @entity28630 @entity1505 @entity205 @entity1140 @entity35
BACKGROUND/AIMS: @entity35 renal inner medullary collecting duct (IMCD) cells are physiologically exposed to a wide range of ambient tonicity. To maintain their function upon changes in osmolality, IMCD cells induce expression of osmoprotective and antiapoptotic genes, mainly mediated by the transcription factor @entity28630 ( @entity28630 ). Some drugs like @entity205 (CsA) are discussed to interfere with the activity of @entity28630 and thereby mediate their nephrotoxic effects. The aim of our study was to further understand CsA @entity137 during elevation of ambient osmolality. METHODS: First we examined @entity137 of CsA in IMCD exposed to elevated tonicity. Employing microarray analysis of gene expression, real-time PCR and immunoassays, we scrutinized pathways contributing to this effect. RESULTS: We show that in IMCD cells CsA but not @entity1140 increases apoptosis upon an increase in tonicity. This effect is independent of cellular @entity28630 localization or activity and reactive @entity26 species. Microarray studies revealed marked quantitative differences in gene expression. Functional analysis showed overrepresentation of genes associated with cell death in presence of CsA. This correlated with increased mRNA expression of genes associated with the death receptor pathway and detection of @entity1505 in culture medium of cells treated with CsA. CONCLUSION: Our results show that CsA @entity137 is induced under elevated ambient osmolality and that death receptor signaling probably contributes to @entity870 @entity137 .
