Down-regulation of transforming growth factor beta receptor type I, II, and III during liver regeneration

Background After partial hepatectomy (PH), it has been shown that hepatocytes are resistant to the mitoinhibitory effects of transforming growth factor beta (TGF-β). Three types of TGF-β receptors have been characterized in mammals. Materials and methods In this study, changes in the protein and mRNA expression of TGF-β types I, II, and III receptors relative to DNA synthesis were studied as a function of time after PH in the rat. Results There was a significant decrease in the protein and mRNA for all three receptor subtypes immediately after PH. All three receptors reached a nadir at 24 hours after PH, which correlated to the time of peak DNA synthesis. The type II receptor recovered to preoperative levels by 120 hours after PH, whereas the types I and III receptors remained at 60% of prehepatectomy levels. Sham-operated rats did not experience a significant drop in receptor protein or mRNA levels. Conclusions This decrease in TGF-β type II receptor expression may account for the reduction in the sensitivity of hepatocytes to TGF-β after PH. Furthermore, the TGF-β receptors appear to represent a class of immediate-early genes that are negatively, rather than positively, regulated after PH