Early induction of nerve growth factor-induced genes after liver resection-reperfusion injury.
OBJECTIVE
Nur-related factor 1 (Nurr1) has been implicated in liver generation after hepatectomy. We hypothesized that the genes in the nerve growth factor-induced gene B (NGFI-B) family was induced in liver ischemia-reperfusion injury.


METHODS
Expression of the NGFI-B family genes was examined by the reverse transcription-polymerase chain reaction in rat and human livers. In situ hybridization was performed to check the localization of the NGFI-B gene in rat liver. Expression of phospho-Ser-133-specific cyclic adenosine-3' :5'-monophosphate response element binding (pCREB) protein was examined by Western blot analysis and gel shift assay, since the promoter region of the NGFI-B family genes contains CRE.


RESULTS
The expression of the NGFI-B family genes were recognized within 30 min after ischemia-reperfusion in rat liver, which was augmented by cycloheximide injection. In human specimens, the NGFI-B family genes expression was stronger than that before ischemic insult. pCREB protein was detected in the rat liver sampled 15 min after reperfusion. Gel shift assay suggested that CREB bound to neuron-derived orphan receptor gene in rat liver cells.


CONCLUSIONS
We recognized the early induction of the NGFI-B family genes after ischemia-reperfusion injury in rat and human livers. A pathway via CREB may be responsible for the induction.
Ohkubo
Takao
T
Hepatobiliary Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Sugawara
Yasuhiko
Y
Sasaki
Kazuki
K
Maruyama
Kouji
K
Ohkura
Naganari
N
Makuuchi
Masatoshi
M
D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000502:physiology; D006498:Hepatectomy; D006801:Humans; D017403:In Situ Hybridization; D008099:Liver / Q000503:physiopathology* / Q000601:surgery; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D015427:Reperfusion Injury / Q000503:physiopathology*; D014157:Transcription Factors / Q000235:genetics*
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C539821:NR4A1 protein, human; C539882:NR4A2 protein, human; C490412:NR4A3 protein, human; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C539820:Nr4a1 protein, rat; C539884:Nr4a2 protein, rat; C091333:Nr4a3 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D014157:Transcription Factors; D001219:Aspartate Aminotransferases