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Normal liver regeneration in p50/nuclear factor κB1 knockout mice
Author(s) -
DeAngelis Robert A.,
Kovalovich Kellen,
Cressman Drew E.,
Taub Rebecca
Publication year - 2001
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2001.23192
Subject(s) - regeneration (biology) , knockout mouse , liver regeneration , p50 , conditional gene knockout , microbiology and biotechnology , medicine , biology , genetics , transcription factor , receptor , phenotype , gene
Nuclear factor κB (NF‐κB) is rapidly activated during liver regeneration following partial hepatectomy or carbon tetrachloride (CCl 4 )‐mediated liver injury and is felt to be important in the antiapoptotic and regenerative responses. After partial hepatectomy, livers of mice deficient in the p50 subunit of NF‐κB (p50 −/− ) showed a loss of NF‐κB and decreased STAT3 transcription factor DNA binding activities. However, nuclear levels of the NF‐κB p65 subunit were increased and peaked earlier in p50 −/− livers. Both messenger RNA and cytoplasmic protein levels of the NF‐κB inhibitor IκBα were lower in p50 −/− livers, potentially accounting for the increase in p65 protein. Small effects on gene expression posthepatectomy were observed in p50 −/− livers, but no effects were seen on hepatocyte DNA synthetic or mitotic responses, serum enzyme levels, or overall liver mass restoration. After CCl 4 treatment, hepatocyte DNA synthesis and mitosis and serum enzyme levels were similar in p50 −/− and p50 +/+ mice, and histologic analysis indicated a slight decrease in overall damage in p50 −/− livers. After injection of Fas antibody, p50 −/− livers showed an earlier onset of nuclear changes consistent with apoptosis. These data indicate that absence of p50 affects certain protein and gene activation pathways following partial hepatectomy, CCl 4 , and Fas treatment but does not impair overall liver regeneration. Interleukin 6 (IL‐6) levels were reduced but still adequate to support regeneration. We hypothesize that increased levels of the NF‐κB p65 subunit in p50 −/− livers may provide compensation for the absence of p50, thereby allowing normal liver regeneration and repair following liver injury.