Severe preservation injury induces Il-6/STAT3 activation with lack of cell cycle progression after partial liver graft transplantation.
Partial liver graft transplantation is a surgical advance developed to overcome severe donor shortage. Survival of these grafts involves recovery from cold ischemia and reperfusion (CIR) injury, immediate regeneration and maintenance of function. Here we examined the outcome of partial liver grafts in comparison to whole grafts following CIR injury. Lewis rats subjected to orthotopic liver transplantation (OLT) with whole grafts preserved in Viaspan were compared to rats receiving 50% and 30% grafts. Outcome was analyzed by survival and regeneration. Transplantation was associated with 100% survival for all grafts, whereas 16 h preservation resulted in 100%, 20% and 0% survival in animals receiving whole, 50% and 30% grafts, respectively. CIR induced increased IL-6 levels in 50% and 30% grafts, and activation of STAT3. Cell cycle progression (cyclin D1) and regeneration (BrdU) was initiated in all livers preserved for 1 or 8 h, but not in partial grafts preserved for 16 h. In conclusion, partial grafts recover from CIR injury through similar molecular pathways to whole grafts. Partial grafts with severe injury fail to achieve cellular proliferation despite the early initiating signals. This failure could be attributed to the impaired ability of the parenchyma to respond to initiating signals for regeneration.
Debonera
Fotini
F
Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Wang
Guodong
G
Xie
Jinfu
J
Que
Xingye
X
Gelman
Andrew
A
Leclair
Cynthia
C
Xin
Dong
D
Shaked
Abraham
A
Olthoff
Kim M
KM
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D019938:Cyclin D1 / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D006085:Graft Survival / Q000276:immunology / Q000502:physiology; D022781:Hepatocytes / Q000166:cytology; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000235:genetics; D016031:Liver Transplantation / Q000276:immunology / Q000379:methods / Q000502:physiology*; D008297:Male; D009926:Organ Preservation; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000235:genetics*
D004268:DNA-Binding Proteins; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D019938:Cyclin D1; D012313:RNA