title: Role of nitric oxide synthesized by nitric oxide synthase 2 in liver regeneration.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kumamoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Togo
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ishibe
authors.forename: Daisuke
authors.initials: D
authors.lastname: Morioka
authors.forename: Kazuteru
authors.initials: K
authors.lastname: Watanabe
authors.forename: Takuji
authors.initials: T
authors.lastname: Takahashi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Shimizu
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Matsuo
authors.forename: Toru
authors.initials: T
authors.lastname: Kubota
authors.forename: Kuniya
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nagashima
authors.forename: Jun
authors.initials: J
authors.lastname: Kawai
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimada
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D015536:Down-Regulation; D015870:Gene Expression; D020868:Gene Silencing; D006498:Hepatectomy; D019394:Ki-67 Antigen / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008115:Liver Regeneration / Q000235:genetics* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D015415:Biomarkers; D019394:Ki-67 Antigen; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse