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 language | English (US) |
|---|---|
| Pages (from-to) | 648-655 |
| Number of pages | 8 |
| Journal | Journal of Surgical Research |
| Volume | 52 |
| Issue number | 6 |
| DOIs | |
| State | Published - 1992 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Surgery
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Transforming growth factor-α (TGF-α) improves hepatic DNA synthesis after hepatectomy in cirrhotic rats. / Kokudo, Norihiro; Kothary, Piyush C.; Eckhauser, Frederic; Raper, Steven E.
In: Journal of Surgical Research, Vol. 52, No. 6, 1992, p. 648-655.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Transforming growth factor-α (TGF-α) improves hepatic DNA synthesis after hepatectomy in cirrhotic rats
AU - Kokudo, Norihiro
AU - Kothary, Piyush C.
AU - Eckhauser, Frederic
AU - Raper, Steven E.
PY - 1992
Y1 - 1992
N2 - 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.
AB - 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.
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U2 - 10.1016/0022-4804(92)90144-O
DO - 10.1016/0022-4804(92)90144-O
M3 - Article
VL - 52
SP - 648
EP - 655
JO - Journal of Surgical Research
JF - Journal of Surgical Research
SN - 0022-4804
IS - 6
ER -