This Article Full Text Full Text (PDF) All Versions of this Article: 144/8/3497    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chabicovsky, M. Articles by Rossmanith, W. Search for Related Content PubMed PubMed Citation Articles by Chabicovsky, M. Articles by Rossmanith, W.

Overexpression of Activin ß_C or Activin ß_E in the Mouse Liver Inhibits Regenerative Deoxyribonucleic Acid Synthesis of Hepatic Cells

Department of Toxicology (M.C., W.R.), Institute for Cancer Research and Neuromuscular Research Department (M.C., W.R.), Institute of Anatomy, University of Vienna, 1090 Vienna, Austria; and Ludwig Boltzmann Institute for Pediatric Endocrinology and Immunology (K.H.), 1090 Vienna, Austria

Address all correspondence and requests for reprints to: Walter Rossmanith, Neuromuscular Research Department, Institute of Anatomy, University of Vienna, Währinger Strasse 13, 1090 Wien, Austria. E-mail: walter.rossmanith{at}univie.ac.at.

Activins are dimeric growth factors composed of ß-subunits, four of which have been isolated so far. Whereas activin ß_A and ß_B are expressed in many tissues, the expression of activin ß_C and ß_E is confined to the liver. To date no biological role or activity has been assigned to activins formed from ß_C or ß_E subunits (activin C and E). Because activin A (ß_Aß_A), among its various functions in other tissues, appears to be a negative regulator of liver growth, we hypothesized a similar role for activin C and E. Using a nonviral gene transfer system we specifically delivered genes encoding activin ß_C, ß_E, or ß_A to the mouse liver. The mRNA analysis and reporter gene coexpression both indicated a reproducible temporal and spatial transgene expression pattern. The effects of activin overexpression were studied in the context of a regenerative proliferation of hepatic cells, a result of the tissue damage associated with the hydrodynamics based gene transfer procedure. Activin ß_C, ß_E, or ß_A expression, all temporarily inhibited regenerative DNA synthesis of hepatocytes and nonparenchymal cells, though to a varying degree. This first report of a biological activity of activin C and E supports an involvement in liver tissue homeostasis and further emphasizes the role of the growing activin family in liver physiology.

This article has been cited by other articles:

				Y.-G. Chen, Q. Wang, S.-L. Lin, C. D. Chang, J. Chung, and S.-Y. Ying Activin Signaling and Its Role in Regulation of Cell Proliferation, Apoptosis, and Carcinogenesis. Experimental Biology and Medicine, May 1, 2006; 231(5): 534 - 544. [Abstract] [Full Text] [PDF]

				U. Muenster, C. A. Harrison, C. Donaldson, W. Vale, and W. H. Fischer An Activin-A/C Chimera Exhibits Activin and Myostatin Antagonistic Properties J. Biol. Chem., November 4, 2005; 280(44): 36626 - 36632. [Abstract] [Full Text] [PDF]

				E J Gold, X Zhang, A M Wheatley, S L Mellor, M Cranfield, G P Risbridger, N P Groome, and J S Fleming {beta}A- and {beta}C-activin, follistatin, activin receptor mRNA and {beta}C-activin peptide expression during rat liver regeneration J. Mol. Endocrinol., April 1, 2005; 34(2): 505 - 515. [Abstract] [Full Text] [PDF]

				J. Gaedeke, T. Boehler, K. Budde, H.-H. Neumayer, and H. Peters Glomerular activin A overexpression is linked to fibrosis in anti-Thy1 glomerulonephritis Nephrol. Dial. Transplant., February 1, 2005; 20(2): 319 - 328. [Abstract] [Full Text] [PDF]

				W. Wada, A. Maeshima, Y.-Q. Zhang, Y. Hasegawa, H. Kuwano, and I. Kojima Assessment of the function of the {beta}C-subunit of activin in cultured hepatocytes Am J Physiol Endocrinol Metab, August 1, 2004; 287(2): E247 - E254. [Abstract] [Full Text] [PDF]

				C. A. Harrison, P. C. Gray, W. H. Fischer, C. Donaldson, S. Choe, and W. Vale An Activin Mutant with Disrupted ALK4 Binding Blocks Signaling via Type II Receptors J. Biol. Chem., July 2, 2004; 279(27): 28036 - 28044. [Abstract] [Full Text] [PDF]

				S. Vejda, N. Erlach, B. Peter, C. Drucker, W. Rossmanith, J. Pohl, R. Schulte-Hermann, and M. Grusch Expression of activins C and E induces apoptosis in human and rat hepatoma cells Carcinogenesis, November 1, 2003; 24(11): 1801 - 1809. [Abstract] [Full Text] [PDF]