Immediate onset of DNA synthesis in remnant rat liver after 90% hepatectomy by an administration of follistatin

Background/Aim: 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, p21(CIP1), p15(INK4B), P27(KIP1), and subunits of activins in fed and starved rats, mRNA for p21(CIP1) and p15(INK4B), but not p27(KIP1) were decreased in 24 h-starved rats compared to the fed rats. mRNA for beta(A) subunit of activin was not detected in either fed or 24-h-starved rats, whereas that for beta(C) subunit was increased in starved rats. Conclusion: These results indicate that follistatin induces immediate onset of DNA synthesis in 90% hepatectomized rats and is quite effective in promoting liver regeneration.