Hepatocyte ‘priming’ and increase in transforming growth factor-β1 mRNA expression are delayed in hypothyroid versus euthyroid rats during liver regeneration
Affiliations: Institute of Biomembranes and Bioenergetics (IBBE), National Research Council (CNR), I-70126 Bari, Italy
- Published online on: June 1, 2006 https://doi.org/10.3892/ijmm.17.6.1063
- Pages: 1063-1068
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Hypothyroidism decreases liver weight and delays the compensatory liver growth after partial hepatectomy (PH) as compared with the euthyroid condition. The aim of this study was to investigate, in hypothyroid rats, the mRNA expression of genes modulating these effects, focusing on c-fos and c-myc, hallmarks of hepatocyte ‘priming’, and on transforming growth factor-β1 (TGF-β1) and its receptor, the transforming growth factor-β1 receptor-type II (TβR-II), negative regulators of liver growth. Euthyroid and hypothyroid male Wistar rats underwent 70% PH and total RNA was isolated from frozen liver samples removed at basal state and during regeneration, 0-144 h after surgery. In this study, we show for the first time that, in the basal liver state, hypothyroidism increased TGF-β1 and TβR-II mRNA levels by 45% and 30%, respectively, as compared with the euthyroid condition and, after PH, resulted in a ≈12-h delay in the activation of c-fos and c-myc mRNA expression. Moreover, the increase in TGF-β1 mRNA levels, detected 24-48 h after PH in euthyroid rats, was delayed by 72 h in hypothyroid rats, occurring when a concomitant reduction in TβR-II was measured. These results suggest that, in hypothyroid rats, at the basal liver level, the increase in mRNA expression of genes that negatively regulate liver growth might be involved in the decrease in liver weight and that, after PH, the delay of hepatocyte ‘priming’ and coordinated changes in mRNA expression of negative regulators of liver regeneration might be involved in delaying the regenerative process.