Effects of proteasome inhibitors on @entity35 renal XXXX in vitro and in vivo.

@entity8 @entity82 @entity1695 @entity16626 @entity19233 @entity1810 @entity35 @entity16628
AIM: @entity1810 ( @entity1810 ) is involved in renal tubulointerstitial @entity82 . Recently, the ubiquitin proteasome system was shown to participate in the @entity1810 signalling pathway. The aim of this study was to examine the effects of proteasome inhibitors on @entity1810 -induced @entity8 and tubular epithelial cells in vitro and on @entity1695 ( @entity1695 ) in vivo. METHODS: @entity35 renal fibroblasts NRK-49F cells and tubular epithelial cells, NRK-52E, were treated with @entity1810 in the presence or absence of a proteasome inhibitor, @entity16626 or @entity16628 . @entity35 were subjected to @entity1695 and received @entity16626 i.p. for 7 days. RESULTS: In cultured renal cells, both @entity16626 and @entity16628 inhibited @entity1810 -induced a-smooth muscle actin (a-SMA) protein expression according to both western blotting and immunofluorescent study results. @entity16626 also suppressed @entity1810 -induced mRNA expression of a-SMA and upregulation of Smad-response element reporter activity. However, @entity16626 did not inhibit @entity1810 -induced phosphorylation and nuclear translocation of @entity19233 . In contrast, @entity16626 increased the protein level of Smad co-repressor SnoN, demonstrating that SnoN is one of the target molecules by which @entity16626 blocks the @entity1810 signalling pathway. Although the proteasome inhibitor suppressed @entity1810 -induced transformation of cultured fibroblasts and tubular epithelial cells, @entity16626 treatment did not ameliorate tubulointerstitial @entity82 in the @entity35 @entity1695 model. CONCLUSION: Proteasome inhibitors attenuate @entity1810 signalling by blocking Smad signal transduction in vitro, but do not inhibit @entity8 in vivo.
