Immediate onset of DNA synthesis in remnant rat liver after 90% hepatectomy by an administration of follistatin.
OBJECTIVE
Follistatin is an antagonist of activins and is effective in promoting liver regeneration after 70% hepatectomy. To examine its efficacy under more critical conditions, we studied the effect of follistatin on liver regeneration in 90% hepatectomized rat.


METHODS
Human recombinant follistatin was infused into the portal vein immediately after 90%, hepatectomy in 24-h-starved rats, and changes in the liver regeneration rate and nuclear bromodeoxyuridine labeling were measured.


RESULTS
In control rats, nuclear labeling was first detected at 11 h of hepatectomy. In follistatin-treated rats, nuclear labeling was markedly increased at 3 h, and was significantly higher than that in control rats at 24, 72, 96, 120 and 144 h. The liver regeneration rate was significantly higher in follistatin-treated rats at 48, 72, 96, 120, 144 and 168 h. To determine the reason for the accelerated growth in starved rats, we compared the expression of mRNA for c-myc, p53, p21CIP1, p15INK4B, p27KIP1, and subunits of activins in fed and starved rats. mRNA for p21CIP1 and p15INK4B, but not p27KIP1 were decreased in 24 h-starved rats compared to the fed rats. mRNA for betaA subunit of activin was not detected in either fed or 24-h-starved rats, whereas that for betaC subunit was increased in starved rats.


CONCLUSIONS
These results indicate that follistatin induces immediate onset of DNA synthesis in 90% hepatectomized rats and is quite effective in promoting liver regeneration.
Kogure
K
K
First Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.
Zhang
Y Q
YQ
Shibata
H
H
Kojima
I
I
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis*; D004353:Drug Evaluation, Preclinical; D038681:Follistatin; D005502:Food; D006023:Glycoproteins / Q000627:therapeutic use*; D006133:Growth Substances / Q000627:therapeutic use*; D006498:Hepatectomy; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects*; D051381:Rats; D013217:Starvation; D013997:Time Factors
D038681:Follistatin; D006023:Glycoproteins; D006133:Growth Substances; D004247:DNA; D001973:Bromodeoxyuridine