Improved hepatic regeneration with reduced injury by redox factor-1 in a rat small-sized liver transplant model.
Redox factor-1 (Ref-1) has been shown to function in a redox-dependent manner in the cell. This study was designed to examine the effects of Ref-1 on liver regeneration as well as protection against postischemic injury in a rat model of 20% partial liver transplantation. Adenovirus carrying the full length of Ref-1 gene was introduced into liver grafts by ex vivo perfusion via the portal vein during preservation. Liver graft weights were assessed, as well as graft histology, serum levels of alanine aminotransferase (ALT)/bilirubin, DNA binding activities of AP-1 and Stat3. Redox factor-1 successfully expressed in the liver graft, improved regeneration by promoting cell proliferation. Overexpression of Ref-1 protein also reduced post-transplant injury and inflammatory reactions in the grafts. The increased serum levels of ALT and bilirubin observed after transplantation were significantly reduced by Ref-1 overexpression. Furthermore, adenovirally overexpressed Ref-1 in mouse liver successfully promoted liver regeneration after simple partial hepatectomy. Interestingly, Ref-1 significantly increased DNA binding of Stat3, but not AP-1. Overexpressed Ref-1 effectively promoted graft regeneration and reduced postischemic injury in a small-sized liver transplantation model. The results of the present study may open a new avenue to clinical transplantation of disproportionately sized grafts in living-related liver transplantation.
Guo
Lei
L
Department of Artificial Organ and Transplantation Surgery, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Haga
Sanae
S
Enosawa
Shin
S
Naruse
Katsutoshi
K
Harihara
Yasushi
Y
Sugawara
Yasuhiko
Y
Irani
Kaikobad
K
Makuuchi
Masatoshi
M
Ozaki
Michitaka
M
D000256:Adenoviridae / Q000235:genetics; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001663:Bilirubin / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D008099:Liver / Q000098:blood supply; D008107:Liver Diseases / Q000378:metabolism / Q000517:prevention & control*; D008115:Liver Regeneration; D016031:Liver Transplantation; D008297:Male; D023421:Models, Animal; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014162:Transfection
D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D000410:Alanine Transaminase; C470319:Apex1 protein, rat; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D001663:Bilirubin