Sustained expression of naked plasmid DNA encoding hepatocyte growth factor in mice promotes liver and overall body growth

Citation
Jw. Yang et al., Sustained expression of naked plasmid DNA encoding hepatocyte growth factor in mice promotes liver and overall body growth, HEPATOLOGY, 33(4), 2001, pp. 848-859
Citations number
42
Categorie Soggetti
Gastroenerology and Hepatology","da verificare
Journal title
HEPATOLOGY
ISSN journal
02709139 → ACNP
Volume
33
Issue
4
Year of publication
2001
Pages
848 - 859
Database
ISI
SICI code
0270-9139(200104)33:4<848:SEONPD>2.0.ZU;2-E
Abstract
To understand the physiological functions of exogenous hepatocyte growth fa ctor (HGF) on normal adult animals, we delivered human HGF gene into mice b y a hydrodynamics-based in vivo gene transfection approach using a naked pl asmid vector. Systemic administration of naked plasmid containing HGF cDNA driven under cytomegalovirus promoter (pCMV-HGF) by rapid injection via the tail vein produced a remarkable level of human HGF protein in the circulat ion, beginning to appear at 4 hours and peaking at 12 hours following injec tion. Tissue distribution studies identified the liver as the organ with th e highest level of transgene expression. Through weekly repeated injections of plasmid vector, we achieved sustained, long-term, high levels of exogen ous HGF expression in mice for 8 weeks. Increases of more than 31% and 16% in liver and body weights were found, respectively, in the mice that receiv ed pCMV-HGF plasmid compared with that given the control vector for 8 weeks . Expression of exogenous HGF in vivo activated mitogen-activated protein k inases and induced proliferating cell nuclear antigen expression in normal adult liver and kidneys. These data suggest that systemic administration of naked plasmid vector is a convenient, safe, and highly efficient approach to introduce and maintain exogenous HGF gene expression in vivo in a contro llable fashion. Our results also indicate that long-term expression of huma n HGF in mice markedly activates growth-related signal transduction events, promotes cell proliferation, and leads to liver and overall body growth in whole adult animals.