Transforming growth factor-α (TGF-α) improves hepatic DNA synthesis after hepatectomy in cirrhotic rats

Norihiro Kokudo, Piyush C. Kothary, Frederic E. Eckhauser, Steven E. Raper

Research output: Contribution to journalArticle

Abstract

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-α (TGF-α), 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/μg DNA (means ± SEM), which was significantly lower than in normal rats (37.3 ± 3.4 cpm/μg DNA, P < 0.05). Exogenous TGF-α (30 nmole/kg, sc every 12 hr) significantly improved [3H]thymidine incorporation (35.6 ± 8.2 cpm/μg DNA, P < 0.05). An autoradiographic nuclear labeling index also confirmed increased DNA synthesis (6.7% vs 13.4%). TGF-α had no effect on normal regenerating liver (42.5 ± 8.8 cpm/μg DNA, NS). Although the significance of TGF-α-enhanced liver regeneration in cirrhosis has yet to be assessed, this model may be useful for the study of mechanisms which control hepatic proliferation.

Original languageEnglish (US)
Pages (from-to)648-655
Number of pages8
JournalJournal of Surgical Research
Volume52
Issue number6
DOIs
StatePublished - Jun 1992

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ASJC Scopus subject areas

  • Surgery

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