NF-kB/ @entity1992 and @entity10182 cooperate to maintain hepatocyte integrity and to prevent development of XXXX .

@entity1 @entity32 @entity1992 @entity8055 @entity82 @entity10182 @entity39 @entity19 @entity5 @entity26 @entity409
BACKGROUND _ AIMS: The liver is frequently challenged by toxins and reactive @entity26 species. Therefore, hepatocytes require cytoprotective strategies to cope with these insults. Since the transcription factors @entity10182 and NF-kB regulate the cellular antioxidant defense system and important survival pathways, we determined their individual and overlapping functions in the liver. METHODS: We generated @entity19 lacking @entity10182 and the NF-kB @entity1992 / @entity1992 subunit in hepatocytes and we analyzed their liver by using histopathology, immunohistochemistry, quantitative RT-PCR, Western blot and Oxyblot analysis. @entity1 @entity8055 ( @entity8055 ) were analyzed by immunohistochemistry. RESULTS: Loss of either @entity10182 or NF-kB/ @entity1992 had only a minor effect on liver homeostasis, but the double knockout @entity19 spontaneously developed @entity409 and @entity82 . Upon aging, more than one-third of the female double mutant @entity19 developed @entity5 , which histologically resemble @entity1 @entity8055 , a @entity5 that predominantly occurs in @entity1 . The @entity19 @entity5 also recapitulated the immunohistochemical marker profile characteristic for @entity1 @entity8055 . Moreover, pNRF2 and NF-kB @entity1992 / @entity1992 was not detectable in the nuclei of @entity8055 @entity5 cells. The @entity19 phenotype was not due to a synergistic effect of both transcription factors on cytoprotective @entity10182 target genes. Rather, loss of @entity10182 or NF-kB/ @entity1992 altered the expression of different genes, and the combination of these alterations likely affects liver homeostasis in the double mutant @entity19 . CONCLUSIONS: Our results provide genetic evidence for a functional cross-talk of @entity10182 and NF-kB/ @entity1992 in hepatocytes, which protects the liver from @entity39 , @entity32 and @entity82 . Furthermore, the double mutant @entity19 represent a valuable animal model for @entity8055 .
