Transforming growth factor-alpha (TGF-alpha) improves hepatic DNA synthesis after hepatectomy in cirrhotic rats.
Impaired liver regeneration in cirrhosis complicates the surgical treatment of liver tumors which arise in this setting. We developed a rat model to investigate the regenerative response of cirrhotic liver after hepatectomy and studied the effect of exogenous transforming growth factor-alpha (TGF-alpha), a potent liver mitogen. Micronodular cirrhosis was established by the simultaneous administration of CCl4 and phenobarbital. Hepatic DNA synthesis ([3H]thymidine incorporation into DNA) 24 hr after partial hepatectomy in cirrhotic rats was 15.6 +/- 3.4 cpm/micrograms DNA (means +/- SEM), which was significantly lower than in normal rats (37.3 +/- 3.4 cpm/micrograms DNA, P less than 0.05). Exogenous TGF-alpha (30 nmol/kg, sc every 12 hr) significantly improved [3H]thymidine incorporation (35.6 +/- 8.2 cpm/micrograms DNA, P less than 0.05). An autoradiographic nuclear labeling index also confirmed increased DNA synthesis (6.7% vs 13.4%). TGF-alpha had no effect on normal regenerating liver (42.5 +/- 8.8 cpm/micrograms DNA, NS). Although the significance of TGF-alpha-enhanced liver regeneration in cirrhosis has yet to be assessed, this model may be useful for the study of mechanisms which control hepatic proliferation.
Kokudo
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N
Department of Surgery, University of Michigan Medical Center, Ann Arbor 48109.
Kothary
P C
PC
Eckhauser
F E
FE
Raper
S E
SE
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D004247:DNA / Q000096:biosynthesis*; D006498:Hepatectomy; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism* / Q000601:surgery; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
D016211:Transforming Growth Factor alpha; D004247:DNA; D002251:Carbon Tetrachloride