Effect of liver regeneration after partial hepatectomy and ischemia-reperfusion on expression of growth factor receptors.
OBJECTIVE
To investigate the effects of experimental partial hepatectomy and normothermic ischemia-reperfusion damage on the time course of the expression of four different growth factor receptors in liver regeneration. This is relevant due to the potential therapeutic use of growth factors in stimulating liver regeneration.


METHODS
For partial hepatectomy (PH) 80% of the liver mass was resected in Sprague Dawley rats. Ischemia and reperfusion (I/R) were induced by occlusion of the portal vein and the hepatic artery for 15 min. The epidermal growth factor receptor, hepatic growth factor receptor, fibroblast growth factor receptor and tumour necrosis factor receptor-1 were analysed by immunohistochemistry up to 72 h after injury. Quantitative RT-PCR was performed at the time point of minimal receptor expression (24 h).


RESULTS
In immunohistochemistry, EGFR, HGFR, FGFR and TNFR1 showed biphasic kinetics after partial hepatectomy with a peak up to 12 h, a nadir after 24 h and another weak increase up to 72 h. During liver regeneration, after ischemia and reperfusion, the receptor expression was lower; the nadir at 24 h after reperfusion was the same. To evaluate whether this nadir was caused by a lack of mRNA transcription, or due to a posttranslational regulation, RT-PCR was performed at 24 h and compared to resting liver. In every probe there was specific mRNA for the receptors. EGFR, FGFR and TNFR1 mRNA expression was equal or lower than in resting liver, HGFR expression after I/R was stronger than in the control.


CONCLUSIONS
At least partially due to a post-transcriptional process, there is a nadir in the expression of the analysed receptors 24 h after liver injury. Therefore, a therapeutic use of growth factors to stimulate liver regeneration 24 h after the damage might be not successful.
Baier
P
P
Department of General and Visceral Surgery, Albert-Ludwigs-University, Freiburg, Germany. peter.baier@uniklinik-freiburg.de
Wolf-Vorbeck
G
G
Hempel
S
S
Hopt
U T
UT
von Dobschuetz
E
E
D000818:Animals; D066246:ErbB Receptors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006133:Growth Substances / Q000494:pharmacology / Q000627:therapeutic use; D006498:Hepatectomy / Q000379:methods; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D008115:Liver Regeneration / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000032:analysis / Q000235:genetics / Q000502:physiology; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors
D006133:Growth Substances; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met