Possible endocrine control by follistatin 315 during liver regeneration based on changes in the activin receptor after a partial hepatectomy in rats.
OBJECTIVE
Activin A is an autocrine inhibitor of cell growth in the liver. The biological activity of activin A is mediated by a heteromeric receptor complex. Follistatin (FS) binds to activin and inhibits its biological effects, and acts as a negative regulator of muscle cells. The role of activin receptors during liver regeneration following a hepatectomy has not been fully assessed. This study investigates the mechanism underlying how activin receptors regulate hepatocyte growth, and the effects of intravenous administration of FS during liver regeneration.


METHODS
The expression of both activins and activin receptors in the liver after a 70% partial hepatectomy (HT) was assessed by RT-PCR and immunohistochemistry. FS 315 or 288 was infused for different periods of time based on changes in hepatocyte activin receptor expression after HT.


RESULTS
Activin receptor expression peaked between 48 and 72 hours after HT. 72 hours after HT, an injection of FS 315 resulted in a more potent stimulation of DNA synthesis and produced a greater increase in body weight compared with the control rats.


CONCLUSIONS
The expression of activin receptors after peak DNA synthesis might be a key component in the downregulation of DNA synthesis. Intravenous administration of FS 315 might promote liver regeneration and have anabolic actions.
Takamura
Kazuhito
K
Department of Digestive Surgery, University of Tokushima Tokushima, Japan. c-ktakamura@eph.pref.ehime.jp
Tsuchida
Kunihiro
K
Miyake
Hidenori
H
Tashiro
Seiki
S
Sugino
Hiromu
H
D030301:Activin Receptors, Type II / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D038681:Follistatin / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D006498:Hepatectomy; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D028322:Inhibin-beta Subunits / Q000187:drug effects / Q000378:metabolism*; D007275:Injections, Intravenous; D008115:Liver Regeneration / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011506:Proteins / Q000187:drug effects / Q000378:metabolism*; D051381:Rats
D038681:Follistatin; C498906:Inhbb protein, rat; D011506:Proteins; C479339:follistatin, 288-amino acid isoform; C103008:inhibin beta A subunit; D028322:Inhibin-beta Subunits; D030301:Activin Receptors, Type II; C425585:activin receptor type II-A