The role of nuclear factor κB in late-gestation liver development in the rat

✍ Scribed by Michelle Embree-Ku; Philip A. Gruppuso

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 406 KB
• Volume: 42
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.20796

✦ Synopsis

During the last 3 days of fetal development in the rodent, a burst of hepatocyte proliferation results in a tripling of liver size. Despite stimulation of mitogenesis via multiple signaling pathways, including some that are considered stress response pathways, little apoptosis accompanies this cell growth. Given the accepted role of nuclear factor B (NF-B) in preventing hepatocellular apoptosis during proliferation in mid-development, we predicted that NF-B would be functional during the period of rapid growth during late gestation in the rat. NF-B binding in electrophoretic mobility shift assays was low in embryonic day (E) 19 liver nuclear extracts relative to adult liver nuclear extracts. An additional band that was present in E19 liver was purified and identified as nucleolin. Tumor necrosis factor ␣ (TNF-␣) administration to E19 embryos in utero produced minimal induction of NF-B p50 homodimers and p50/p65 heterodimers, yet baseline apoptosis was not affected. Although p65 was present in E19 hepatocyte cytoplasm in amounts comparable to adult liver, we observed little translocation of p65 to the liver nuclei following TNF-␣ administration. Additionally, expression of several NF-B-responsive genes remained minimally induced in E19 liver following TNF-␣ treatment. In conclusion, although the NF-B components are present in late-gestation fetal liver, NF-B as a transcription factor is relatively inactive and unresponsive to TNF-␣. Given this finding and the high level of proliferation in lategestation fetal liver, we predict that alternative antiapoptotic mechanisms are active during this period of rapid hepatic growth. (HEPATOLOGY 2005;42:326-334.