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PMID:9699514

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Citation

Nishikawa, Y, Wang, M and Carr, BI (1998) Changes in TGF-beta receptors of rat hepatocytes during primary culture and liver regeneration: increased expression of TGF-beta receptors associated with increased sensitivity to TGF-beta-mediated growth inhibition. J. Cell. Physiol. 176:612-23

Abstract

To clarify the role of transforming growth factor-beta (TGF-beta) and its receptors in hepatocyte growth, we studied the expression of TGF-beta1 and its receptors and the sensitivity to growth inhibition by TGF-beta1 protein in rat hepatocytes derived from resting and regenerating livers. In hepatocytes derived from resting livers, mRNAs for TGF-beta type II receptor (TbetaR-II), insulin-like growth factor-II/mannose 6-phosphate receptor (IGF-II/M-6-PR), and TGF-beta1 increased with time in primary culture. The cell surface TGF-beta receptor proteins (TbetaR-I, II, and III), examined by the receptor affinity-labeling assay using 125I-TGF-beta1, also increased, especially after 48 hr of culture. Hepatocytes were more sensitive to inhibition of DNA synthesis, when the TGF-beta1 protein was added at later times in culture, corresponding to the presence of increased TGF-beta receptors. In hepatocytes from regenerating livers after a partial hepatectomy (PH), an increase of TbetaR-I, TbetaR-II, TbetaR-III, IGF-II/M-6-PR, and TGF-beta1 mRNAs was found, compared with hepatocytes from resting livers. Similarly, using TGF-beta receptor affinity-labeling assay, hepatocytes from PH livers were found to have an increase in TbetaR-I, II, and III proteins, with a peak at 4 days post-PH, compared with hepatocytes from resting livers. When TGF-beta1 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-beta receptors and sensitivity to growth inhibition by TGF-beta1 protein change together and are modulated during liver regeneration, as well as during the conditions of primary culture.

Links

PubMed Online version:<612::AID-JCP18>3.0.CO;2-0 10.1002/(SICI)1097-4652(199809)176:3<612::AID-JCP18>3.0.CO;2-0

Keywords

Activin Receptors, Type I; Animals; Blotting, Northern; Cells, Cultured; DNA/biosynthesis; Gene Expression/physiology; Growth Inhibitors/genetics; Growth Inhibitors/pharmacology; Liver/chemistry; Liver/cytology; Liver Regeneration/drug effects; Liver Regeneration/physiology; Male; Protein-Serine-Threonine Kinases/genetics; RNA, Messenger/analysis; Rats; Rats, Inbred F344; Receptors, Transforming Growth Factor beta/genetics; Transforming Growth Factor beta/genetics; Transforming Growth Factor beta/pharmacology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:TGBR3

involved_in

GO:0031100: animal organ regeneration

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:TGFR2

involved_in

GO:0031100: animal organ regeneration

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:TGFR1

involved_in

GO:0031100: animal organ regeneration

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:TGFB1

involved_in

GO:0031100: animal organ regeneration

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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