Yang Liu, Magness Scott T, Bataller Ramon, Rippe Richard A, Brenner David A
Dept. of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
Am J Physiol Gastrointest Liver Physiol. 2005 Sep;289(3):G530-8. doi: 10.1152/ajpgi.00526.2004. Epub 2005 May 19.
The transcription factor nuclear factor-kappaB (NF-kappaB) is activated during liver regeneration after partial hepatectomy. However, the physiological role and cellular localization of NF-kappaB activation are unresolved. In this study, we used an adenoviral vector expressing a mutated form of IkappaBalpha to inhibit NF-kappaB activity during liver regeneration. After partial hepatectomy in mice, introduction of Ad5IkappaB, but not a control virus (Ad5GFP), resulted in increased liver injury and decreased hepatocyte proliferation. Hepatocyte apoptosis was not observed. To investigate the kinetics and cellular localization of NF-kappaB-induced transcription during liver regeneration, we generated a transgenic mouse expressing enhanced green fluorescent protein (EGFP) under the transcriptional control of NF-kappaB cis elements (cis-NF-kappaB-EGFP). During liver regeneration, EGFP expression was detected within 12 h and was primarily located in Kupffer cells. Our data demonstrate that activation of NF-kappaB initially occurs in Kupffer cells after partial hepatectomy in mice.
转录因子核因子-κB（NF-κB）在部分肝切除术后的肝脏再生过程中被激活。然而，NF-κB激活的生理作用和细胞定位仍未明确。在本研究中，我们使用表达突变形式的IkappaBalpha的腺病毒载体来抑制肝脏再生过程中的NF-κB活性。在小鼠部分肝切除术后，导入Ad5IkappaB而非对照病毒（Ad5GFP），导致肝损伤加重且肝细胞增殖减少。未观察到肝细胞凋亡。为了研究肝脏再生过程中NF-κB诱导转录的动力学和细胞定位，我们构建了一种在NF-κB顺式元件（cis-NF-κB-EGFP）转录控制下表达增强型绿色荧光蛋白（EGFP）的转基因小鼠。在肝脏再生过程中，EGFP表达在12小时内即可检测到，且主要位于库普弗细胞中。我们的数据表明，小鼠部分肝切除术后，NF-κB的激活最初发生在库普弗细胞中。
