Overexpression of NK2 inhibits liver regeneration after partial hepatectomy in mice.
OBJECTIVE
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-alpha (TNF-alpha) and interleukin-6 (IL-6) in liver tissues were prolonged in NK2 transgenic mice that died after PH.


CONCLUSIONS
Our findings indicate that over-expression of NK2 inhibits liver regeneration after PH.
Otsuka
Toshiyuki
T
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
Horiguchi
Norio
N
Kanda
Daisuke
D
Kosone
Takashi
T
Yamazaki
Yuichi
Y
Yuasa
Kazuhisa
K
Sohara
Naondo
N
Kakizaki
Satoru
S
Sato
Ken
K
Takagi
Hitoshi
H
Merlino
Glenn
G
Mori
Masatomo
M
D000818:Animals; D002455:Cell Division / Q000502:physiology; D005260:Female; D015870:Gene Expression; D006498:Hepatectomy / Q000379:methods*; D017228:Hepatocyte Growth Factor / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000502:physiology* / Q000601:surgery; D008115:Liver Regeneration / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D017434:Protein Structure, Tertiary
D017228:Hepatocyte Growth Factor