Changes in activin and activin receptor subunit expression in rat liver during the development of CCl4-induced cirrhosis

Amounts of betaA-activin, betaC-activin, activin receptor subunits ActRIIA and ActRIIB mRNA, and betaA- and betaC-activin subunit protein immunoreactivity were investigated in male Lewis rats, either untreated or after 5 or 10 weeks of CCl4 treatment to induce cirrhosis. Apoptosis was assessed histologically and with an in situ cell death detection kit (TUNEL). Reverse transcription and polymerase chain reaction were used to evaluate mRNA levels. Activin betaA- and betaC-subunit immunoreactivity was studied by immunohistochemistry using specific monoclonal antibodies. Hepatocellular apoptosis (P < 0.001), increased betaA- and betaC-activin mRNAs (three- to fourfold; P < 0.01) and increased betaA- and betaC-activin tissue immunoreactivity were evident, whereas ActRIIA mRNA concentrations fell (30%; P < 0.01) after 5 weeks of CCl4 treatment. The mRNA concentrations at 10 weeks were not significantly different from controls, despite extensive hepatic nodule formation. We conclude that the increased activin subunit expression is associated with apoptosis, rather than hepatic fibrosis and nodule formation. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.