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
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.