DOWN-REGULATION OF TRANSFORMING GROWTH-FACTOR-BETA RECEPTOR TYPE-I, TYPE-II, AND TYPE-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-beta). Three types of TGF-beta receptors have been characterized in mammals. MATERIALS AND METHODS: In this study, changes in the protein and mRNA expression of TGF-beta 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-beta type II receptor expression may account for the reduction in the sensitivity of hepatocytes to TGF-beta after PH. Furthermore, the TGF-beta receptors appear to represent a class of immediate-early genes that are negatively, rather than positively, regulated after PH.