Activin A: an autocrine inhibitor of initiation of DNA synthesis in rat hepatocytes. (original) (raw)
Research Article Free access | 10.1172/JCI116727
T Mine, H Shibata, Y Eto, Y Hasegawa, T Takeuchi, S Asano, and I Kojima
Cell Biology Research Unit, Gunma University, Maebashi, Japan.
Find articles by Yasuda, H. in:PubMed |Google Scholar
Cell Biology Research Unit, Gunma University, Maebashi, Japan.
Find articles by Mine, T. in:PubMed |Google Scholar
Cell Biology Research Unit, Gunma University, Maebashi, Japan.
Find articles by Shibata, H. in:PubMed |Google Scholar
Cell Biology Research Unit, Gunma University, Maebashi, Japan.
Find articles by Eto, Y. in:PubMed |Google Scholar
Cell Biology Research Unit, Gunma University, Maebashi, Japan.
Find articles by Hasegawa, Y. in:PubMed |Google Scholar
Cell Biology Research Unit, Gunma University, Maebashi, Japan.
Find articles by Takeuchi, T. in:PubMed |Google Scholar
Cell Biology Research Unit, Gunma University, Maebashi, Japan.
Find articles by Asano, S. in:PubMed |Google Scholar
Cell Biology Research Unit, Gunma University, Maebashi, Japan.
Find articles by Kojima, I. in:PubMed |Google Scholar
Published September 1, 1993 -More info
Published September 1, 1993 -Version history
The present study was conducted to examine the effect of activin A on growth of rat hepatocytes. EGF induced a 10-fold increase in DNA synthesis as assessed by [3H]thymidine incorporation in cultured hepatocytes. When activin A was added together with EGF, DNA synthesis induced by EGF was markedly inhibited. Inhibition was detected at a concentration of 10(-10) M, and 5 x 10(-9) M activin A almost completely blocked EGF-mediated DNA synthesis. Similarly, activin A completely blocked DNA synthesis induced by hepatocyte growth factor/scatter factor. Activin A was capable of inhibiting EGF-mediated DNA synthesis, even when added 36 h after the addition of EGF. With the same time interval, TGF-beta also blocked EGF-induced DNA synthesis. Although both activin A and TGF-beta inhibited growth of hepatocytes in a similar manner, either activin A or TGF-beta did not compete with each other in their binding when assessed by competitive binding using an iodinated ligand. When hepatocytes were incubated with EGF, release of bioactivity of activin A into culture medium was detected after 48 h or later. Activity of activin A was released from parenchymal cells but not from nonparenchymal cells. mRNA for beta A subunit of activin was detected only slightly in unstimulated hepatocytes, but markedly increased at 48 h after the addition of EGF. To determine whether endogenously produced activin A affects DNA synthesis, we examined the effect of follistatin, an activin-binding protein that blocks the action of activin A. An addition of follistatin significantly enhanced EGF-induced DNA synthesis. Finally, in partial hepatectomized rat, expression of mRNA for beta A subunit in liver was markedly increased 24 h after the partial hepatectomy. These results indicate that activin A inhibits initiation of DNA synthesis in hepatocytes by acting on its own receptor and that activin A acts as an autocrine inhibitor of DNA synthesis in rat hepatocytes.
Images.
Click on an image below to see the page. View PDF of the complete article
- Version 1 (September 1, 1993): No description