Role of nitric oxide synthesized by nitric oxide synthase 2 in liver regeneration
Article first published online: 1 APR 2008
© 2008 The Authors. Journal compilation © 2008 Blackwell Munksgaard
Volume 28, Issue 6, pages 865–877, July 2008
How to Cite
Kumamoto, T., Togo, S., Ishibe, A., Morioka, D., Watanabe, K., Takahashi, T., Shimizu, T., Matsuo, K.-i., Kubota, T., Tanaka, K., Nagashima, Y., Kawai, J., Hayashizaki, Y. and Shimada, H. (2008), Role of nitric oxide synthesized by nitric oxide synthase 2 in liver regeneration. Liver International, 28: 865–877. doi: 10.1111/j.1478-3231.2008.01712.x
- Issue published online: 4 JUN 2008
- Article first published online: 1 APR 2008
- Received 10 October 2007Accepted 15 January 2008
- liver regeneration;
- nitric oxide;
- nitric oxide synthase
Background/Aims: Nitric oxide synthase 2 (NOS2) is expressed during liver regeneration after a partial hepatectomy (PHx); NOS2 subsequently synthesizes nitric oxide (NO). However, the role of NOS2-synthesized NO in post-PHx liver regeneration remains unclear. We investigated the role of NOS2-synthesized NO in liver regeneration.
Methods: NOS2 knockout (NOS2-KO) mice and control mice were subjected to PHx. Liver mass recovery and serum alanine aminotransferase (ALT) levels were then evaluated. The expressions of Ki-67 and single-strand DNA were also evaluated in remnant liver specimens. Differences in the gene expression profiles of the two groups of remnant liver specimens were analysed using a microarray and were validated using a reverse transcription-polymerase chain reaction (RT-PCR).
Results: In NOS2-KO mice, liver regeneration was delayed and apoptosis and serum ALT levels were higher than the levels in the control mice. A microarray study and RT-PCR revealed that heat shock protein 70 family (HSP70 family), haeme oxygenase 1 (Hmox1), neuropilin 1 (Nrp1) and epidermal growth factor receptor (EGFR) were downregulated in NOS2-KO mice.
Conclusions: NOS2-synthesized NO may improve hepatocyte viability through the induction of the HSP70 family and Hmox1 and may sensitize the remnant liver to growth factors through the induction of Nrp1 and EGFR post-PHx.