Biphasic activation of liver regeneration-associated signals in an early stage after portal vein branch ligation
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya (Japan)
- Department of Physiology, Nagoya University Graduate School of Medicine, Nagoya (Japan) and Cell Mechanosensing, Japan Science and Technology Corporation, Nagoya (Japan) and Department of Molecular Physiology, National Institute for Physiological Science, Okazaki (Japan)
At an early stage in liver regeneration, a variety of factors including transcriptional factors, proinflammatory cytokines, and proto-oncogenes are activated or expressed. However, these responses are affected by surgical stress in the conventional portal vein branch ligation model (PVL). We sought to determine the net activation of early regeneration-associated signals after PVL using a newly developed non-surgical stress PVL model. Male Wistar rats were assigned into two groups, a stress-PVL (sPVL) model with laparotomy and portal vein branch ligation, and a non-stress-PVL (nsPVL) one subjected to portal vein branch ligation 1 week after laparotomy in which the effects of surgical stress were subsided. The activation of transcriptional factors and expression of immediate early genes were analyzed at an early time point (within 24 h) by Western blotting and RT-PCR, respectively. A monophasic upregulation of nuclear factor-{kappa}B (NF-{kappa}B) and phosphorylated-signal transducer and activator of transcription 3 (p-STAT3) peaked at 3 h after sPVL was observed. In contrast, the expression pattern of these factors was biphasic (first peak at 0.5-1 h, second peak at 3-6 h) in nsPVL group. The expression pattern of immediate early genes showed a similar trend between sPVL and nsPVL. cDNA array analysis for the non-ligated lobe at 2 h after PVL revealed a much higher gene activation in sPVL than in nsPVL. These results indicate that previously observed activation pattern of regeneration-associated signals after PVL is significantly affected by the effect of laparotomy and our results using nsPVL model may more accurately represent liver regeneration-associated signal pattern.
- OSTI ID:
- 20854528
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 349, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2006.08.083; PII: S0006-291X(06)01897-3; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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