Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2005; 11(47): 7444-7449
Published online Dec 21, 2005. doi: 10.3748/wjg.v11.i47.7444
Overexpression of NK2 inhibits liver regeneration after partial hepatectomy in mice
Toshiyuki Otsuka, Norio Horiguchi, Daisuke Kanda, Takashi Kosone, Yuichi Yamazaki, Kazuhisa Yuasa, Naondo Sohara, Satoru Kakizaki, Ken Sato, Hitoshi Takagi, Glenn Merlino, Masatomo Mori
Toshiyuki Otsuka, Norio Horiguchi, Daisuke Kanda, Takashi Kosone, Yuichi Yamazaki, Kazuhisa Yuasa, Naondo Sohara, Satoru Kakizaki, Ken Sato, Hitoshi Takagi, Masatomo Mori, Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15 Showa, Maebashi, Gunma 371-8511, Japan
Glenn Merlino, Laboratory of Cell Regulation and Car-cinogenesis, National Cancer Institute, Building 37, Room 5002, Bethesda, MD 20892-4264, United States
Author contributions: All authors contributed equally to the work.
Correspondence to: Hitoshi Takagi, Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15 Showa, Maebashi, Gunma 371-8511, Japan. htakagi@med.gunma-u.ac.jp
Telephone: +81-27-220-8127 Fax: +81-27-220-8136
Received: March 28, 2005
Revised: May 1, 2005
Accepted: May 3, 2005
Published online: December 21, 2005
Abstract

AIM: To investigate the in vivo effects of NK2 on liver regeneration after partial hepatectomy (PH).

METHODS: Survival after PH was observed with 21 NK2 transgenic mice and 23 wild-type (WT) mice over 10 d. Liver regeneration was analyzed using histology and immunohistochemistry. Expressions of genes were analyzed using Northern blot analysis, immunoprecipitation and immunoblotting, and reverse transcriptase polymerase chain reaction assay. Kaplan-Meier method and the log-rank test were used for analyzing the survival after PH. Differences in the results of immunohistochemistry and percentage of liver regeneration was determined by the Student’s t-test.

RESULTS: More than half of NK2 transgenic mice died within 48 h after PH. After PH, increased deposition of small lipid droplets in hepatocytes was evident and hepatic proliferation was inhibited in NK2 transgenic mice. The hepatic expression and kinase activity of HGF receptor, c-Met, were unchanged among WT mice and NK2 transgenic mice after PH. The expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in liver tissues were prolonged in NK2 transgenic mice that died after PH.

CONCLUSION: Our findings indicate that over-expression of NK2 inhibits liver regeneration after PH.

Keywords: Hepatocyte growth factor; NK2; Transgenic mice; Partial hepatectomy; Liver regeneration