Changes in TGF-β receptors of rat hepatocytes during primary culture and liver regeneration: Increased expression of TGF-β receptors associated with increased sensitivity to TGF-β-mediated growth inhibition
✍ Scribed by Yuji Nishikawa; Meifang Wang; Brian I. Carr
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 330 KB
- Volume
- 176
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
To clarify the role of transforming growth factor-b (TGF-b) and its receptors in hepatocyte growth, we studied the expression of TGF-b1 and its receptors and the sensitivity to growth inhibition by TGF-b1 protein in rat hepatocytes derived from resting and regenerating livers. In hepatocytes derived from resting livers, mRNAs for TGF-b type II receptor (TbR-II), insulin-like growth factor-II/mannose 6-phosphate receptor (IGF-II/M-6-PR), and TGF-b1 increased with time in primary culture. The cell surface TGF-b receptor proteins (TbR-I, II, and III), examined by the receptor affinity-labeling assay using 125 I-TGF-b1, also increased, especially after 48 hr of culture. Hepatocytes were more sensitive to inhibition of DNA synthesis, when the TGF-b1 protein was added at later times in culture, corresponding to the presence of increased TGF-b receptors. In hepatocytes from regenerating livers after a partial hepatectomy (PH), an increase of TbR-I, TbR-II, TbR-III, IGF-II/M-6-PR, and TGF-b1 mRNAs was found, compared with hepatocytes from resting livers. Similarly, using TGF-b receptor affinity-labeling assay, hepatocytes from PH livers were found to have an increase in TbR-I, II, and III proteins, with a peak at 4 days post-PH, compared with hepatocytes from resting livers. When TGF-b1 protein was added for a short period (6 or 24 hr) after cell attachment to hepatocyte cultures, it inhibited DNA synthesis more effectively in hepatocytes from regenerating compared with resting livers. Our results show that hepatocyte TGF-b receptors and sensitivity to growth inhibition by TGF-b1 protein change together and are modulated during liver regeneration, as well as during the conditions of primary culture.