Hepatic regenerative response in small-sized liver isografts in the rat.
BACKGROUND
To investigate hepatic regenerative response and associated mechanisms in different-size liver grafts in the rat.


METHODS
Rat models of different-size-graft liver transplantation (whole, 50%-size, or 30%-size) were established, with a sham operation group serving as a control. Portal pressure, graft injury, interleukin 6 (IL-6), signal transducer and activator of transcription (Stat3), mitogen-activated protein kinase (MAPK), cyclin D1, and proliferating cell nuclear antigen (PCNA) were all assessed.


RESULTS
The portal pressure was significantly higher and hepatic injury more severe in the smaller sized groups than in the whole graft group, especially in the 30%-size grafts. Hepatic IL-6 and tumor necrosis factor-alpha (TNF-alpha) levels in the two smaller sized groups were significantly higher than in the whole graft group, while IL-6 levels appeared to be negatively associated with graft sizes. Downstream markers of IL-6, Stat3 and MAPK phosphorylation, cyclin D1, and PCNA expression were also markedly increased in the small-sized grafts compared with the whole grafts, and appeared to positively correlate with early measurements of portal pressure and subsequent hepatic injury.


CONCLUSIONS
Vigorous hepatic regeneration in small-for-size liver grafts may be associated with highly activated IL-6/Stat3 and MAPK signaling, which may in turn correlate with graft size, portal pressure, and hepatic injury.
Yao
Ai Hua
AH
Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Yang
Yan
Y
Li
Xiang Cheng
XC
Pu
Li Yong
LY
Zhong
Ji Wei
JW
Liu
Xian Zhong
XZ
Yu
Yue
Y
Zhang
Feng
F
Kong
Lian Bao
LB
Wang
Xue Hao
XH
D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D019938:Cyclin D1 / Q000032:analysis; D006439:Hemodynamics; D006975:Hypertension, Portal / Q000209:etiology / Q000503:physiopathology; D015850:Interleukin-6 / Q000032:analysis; D008099:Liver / Q000033:anatomy & histology* / Q000201:enzymology; D008115:Liver Regeneration / Q000502:physiology*; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000032:analysis; D017082:Portal Pressure; D011169:Portal Vein / Q000502:physiology; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000503:physiopathology; D050796:STAT3 Transcription Factor / Q000032:analysis
D015850:Interleukin-6; D018809:Proliferating Cell Nuclear Antigen; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D019938:Cyclin D1; D020929:Mitogen-Activated Protein Kinase Kinases