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

J Hepatol. 1998 Dec;29(6):977-84. doi: 10.1016/s0168-8278(98)80126-8.


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, 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.

Conclusion: These results indicate that follistatin induces immediate onset of DNA synthesis in 90% hepatectomized rats and is quite effective in promoting liver regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bromodeoxyuridine / metabolism
  • Cell Nucleus / metabolism
  • DNA / biosynthesis*
  • Drug Evaluation, Preclinical
  • Follistatin
  • Food
  • Glycoproteins / therapeutic use*
  • Growth Substances / therapeutic use*
  • Hepatectomy
  • Humans
  • Liver / drug effects*
  • Liver / metabolism
  • Liver Regeneration / drug effects*
  • Rats
  • Starvation
  • Time Factors


  • Follistatin
  • Glycoproteins
  • Growth Substances
  • DNA
  • Bromodeoxyuridine