Transforming growth factor β and activin tonically inhibit DNA synthesis in the rat liver
| Autor: | Yoshihisa Hasegawa, Masatomo Mori, Takeshi Ichikawa, Kimitaka Kogure, You-Qing Zhang, Hitoshi Takagi, Itaru Kojima |
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| Rok vydání: | 2001 |
| Předmět: |
Male
medicine.medical_specialty Activin Receptors Apoptosis Biology Transforming Growth Factor beta Internal medicine medicine Animals Protein Isoforms Rats Wistar Receptor Genes Dominant Inhibin-beta Subunits Cell Nucleus Hepatology DNA synthesis Cell growth Gene Transfer Techniques DNA Organ Size Activin receptor Immunohistochemistry Activins Rats Endocrinology medicine.anatomical_structure Bromodeoxyuridine Liver Terminal deoxynucleotidyl transferase Hepatocyte Receptors Transforming Growth Factor beta Transforming growth factor |
| Zdroj: | Hepatology. 34:918-925 |
| ISSN: | 0270-9139 |
| DOI: | 10.1053/jhep.2001.29132 |
| Popis: | The present study was conducted to assess the role of transforming growth factor beta (TGF-beta) and activin(s) in the regulation of the mass of the liver. To this end, we eliminated TGF-beta or activin signaling in intact rat liver by adenovirus-mediated transfer of the gene encoding truncated type II TGF-beta receptor (AdextTR) or truncated type II activin receptor (AdextAR). In intact rat liver that received a single application of either AdextTR or AdextAR via the portal vein, DNA synthesis as assessed by bromodeoxy uridine (BrdU) labeling was induced. In AdextTR- or AdextAR-treated rats, nuclear labeling was significantly higher than that in AdexLacZ, adenovirus vector encoding Escherichia coli beta-galactosidase gene, or saline-treated rats at 3, 5, 7, and 9 days of infusion. The peak of the BrdU labeling was observed after 7 days of infusion and the labeling decreased thereafter. Apoptosis of hepatocytes, assessed by the terminal deoxynucleotidyl transferase (TdT)-mediated, dUTP-biotin nick-end labeling method was detected after 9 days of infusion. Immunoreactivity of TGF-beta and activin A increased in the liver after the blockade of the activin or TGF-beta signaling. TGF-beta and activin A may have been up-regulated when the action of these ligands was blocked. These results indicate that blockade of the action of either TGF-beta or activin leads to the initiation of DNA synthesis in intact liver. TGF-beta and activin tonically inhibit hepatocyte growth even in intact liver and may play a critical role in the maintenance of constant liver mass. |
| Databáze: | OpenAIRE |
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