A SINGLE INTRAPORTAL ADMINISTRATION OF FOLLISTATIN ACCELERATES LIVER-REGENERATION IN PARTIALLY HEPATECTOMIZED RATS

Background/Aims: Activin A is an autocrine negative regulator of DNA s ynthesis in rat hepatocytes and is expressed in remnant liver after pa rtial hepatectomy. To determine the role of activin A in liver regener ation, the effects of exogenous follistatin, which blocks the action o f activin A, were examined. Methods: Human recombinant follistatin was infused into the portal Vein immediately after 70% hepatectomy. Chang es in body weight, remnant liver weight, liver regeneration rate, and nuclear bromodeoxyuridine labeling were measured. Results: In control rats, nuclear labeling was observed at 24 hours and peaked at 36 hours after the hepatectomy. In follistatin-treated rats, nuclear labeling was first observed after 18 hours and was significantly (P < 0.05) gre ater than that in control rats at 24 hours. In follistatin-treated rat s, both remnant liver weight and river regeneration rate were signific antly greater at 120 hours. Serum concentrations of albumin and glucos e remained reduced for up to 120 hours in control rats but recovered i n follistatin-treated rats. Conclusion: A single administration of fol listatin accelerates the initial round of DNA synthesis after partial hepatectomy. Activin A produced in remnant liver may exert tonic inhib itory effect on liver regeneration. Follistatin may be useful as a pot ential therapeutic agent to promote liver regeneration.