Title: Adenovirus-mediated overexpression of follistatin enlarges intact liver of adult rats
Abstract: HepatologyVolume 38, Issue 5 p. 1107-1115 Original ArticleFree Access Adenovirus-mediated overexpression of follistatin enlarges intact liver of adult rats Kazuaki Takabe, Kazuaki Takabe The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, CASearch for more papers by this authorLili Wang, Lili Wang Laboratory of Genetics, The Salk Institute, La Jolla, CASearch for more papers by this authorAngela M. O. Leal, Angela M. O. Leal The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, CASearch for more papers by this authorLeigh A. MacConell, Leigh A. MacConell The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, CASearch for more papers by this authorEzra Wiater, Ezra Wiater The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, CASearch for more papers by this authorTomoaki Tomiya, Tomoaki Tomiya First Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo, JapanSearch for more papers by this authorAkihiko Ohno, Akihiko Ohno First Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo, JapanSearch for more papers by this authorInder M. Verma, Inder M. Verma Laboratory of Genetics, The Salk Institute, La Jolla, CASearch for more papers by this authorWylie Vale Ph.D., Corresponding Author Wylie Vale Ph.D. [email protected] The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, CAThe Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037. fax: 858-552-1546===Search for more papers by this author Kazuaki Takabe, Kazuaki Takabe The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, CASearch for more papers by this authorLili Wang, Lili Wang Laboratory of Genetics, The Salk Institute, La Jolla, CASearch for more papers by this authorAngela M. O. Leal, Angela M. O. Leal The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, CASearch for more papers by this authorLeigh A. MacConell, Leigh A. MacConell The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, CASearch for more papers by this authorEzra Wiater, Ezra Wiater The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, CASearch for more papers by this authorTomoaki Tomiya, Tomoaki Tomiya First Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo, JapanSearch for more papers by this authorAkihiko Ohno, Akihiko Ohno First Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo, JapanSearch for more papers by this authorInder M. Verma, Inder M. Verma Laboratory of Genetics, The Salk Institute, La Jolla, CASearch for more papers by this authorWylie Vale Ph.D., Corresponding Author Wylie Vale Ph.D. [email protected] The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, CAThe Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037. fax: 858-552-1546===Search for more papers by this author First published: 30 December 2003 https://doi.org/10.1053/jhep.2003.50483Citations: 30AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract Under normal physiologic conditions, liver size is under strict regulatory control. Activin, a member of the transforming growth factor β (TGF-β) superfamily, is expressed in the intact adult liver and is an inhibitor of hepatocyte growth. However, the exact role played by endogenous activin in maintaining the size of a normal adult liver has yet to be completely examined in vivo. Here, we report the development of an adenoviral vector (AdexCAFS288) that expressed human follistatin-288, which binds to activin and neutralizes its biologic activities. AdexCAGFP, a control virus, expressed green fluorescent protein. AdexCAFS288 effectively expressed follistatin-288, as measured both in HepG2 cell lysate and conditioned medium and blocked activin signaling and its biologic functions in vitro. Intraperitoneal injection of AdexCAFS288 in vivo resulted in significant liver growth (146% of control) in intact liver of adult male rats 12 days following treatment without significant dysfunctions. The increase in liver size was attributed to increased hepatocyte proliferation, as monitored by the mitotic index. Furthermore, there was a significant correlation between serum follistatin levels and liver weight. In conclusion, our results suggest that activin plays a critical role in maintaining optimal liver size and implicates the endogenous activin system as a therapeutic target in the treatment of liver disease. References 1 Van Thiel D, Gavaler J, Kam I, Francavilla A, Polimeno L, Schade R, Smith J, et al. Rapid growth of an intact human liver transplanted into a recipient larger than the donor. Gastroenterology 1987; 93: 1414– 1419. 2 Higgins G, Anderson R. Experimental pathology of the liver of the white rat following partial surgical removal. 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