PMID- 10859026
OWN - NLM
STAT- MEDLINE
DCOM- 20000822
LR  - 20180821
IS  - 1076-1551 (Print)
IS  - 1528-3658 (Electronic)
IS  - 1076-1551 (Linking)
VI  - 6
IP  - 2
DP  - 2000 Feb
TI  - Intravenous injection of an adenovirus encoding hepatocyte growth factor results 
      in liver growth and has a protective effect against apoptosis.
PG  - 96-103
AB  - BACKGROUND: Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic 
      cytokine with mitogenic, motogenic and morphogenic effects for a wide variety of 
      cells. Previous studies have reported that the in vivo infusion in normal, 
      untreated mice of recombinant HGF results in low levels of DNA synthesis and 
      liver proliferation. In this study, we examined whether liver regeneration could 
      be obtained by the in vivo injection of a recombinant adenoviral vector encoding 
      human HGF (Ad.CMV.rhHGF) in normal, intact mice. MATERIALS AND METHODS: C57BL/6 
      mice were infused intravenously with doses increasing from 1 to 4 x 1011 
      particles of the recombinant human HGF (rhHGF) adenoviral vector or with a 
      control virus encoding Escherichia coli beta-galactosidase (Ad.CMV.lacZ). At day 
      5, mice were sacrificed and evaluated for the presence of hepatocyte mitogenesis 
      and liver regeneration (5-bromo-2'-deoxyuridine (BrdU) assays and liver weight 
      determination) and for the presence of liver damage (serum alanine 
      amino-transferase (ALT) measurements and TUNEL assays). RESULTS: In vivo 
      administration of rhHGF stimulated DNA synthesis of hepatocytes and liver weight 
      in a dose-dependent fashion. The maximal effect was seen after the infusion of 3 
      x 1011 particles which resulted at day 5 in >130% increase in relative liver mass 
      with little cytopathic effect. In contrast, administration of the lacZ adenoviral 
      vector caused little hepatocyte replication, but induced high levels of serum ALT 
      (approximately 3 times higher than the rhHGF vector) and significant apoptotic 
      cell death. CONCLUSIONS: This study shows that a single injection of Ad.CMV.rhHGF 
      alone is able to induce in vivo and in a very short period of time, robust DNA 
      synthesis and liver proliferation in normal mice without liver injury or partial 
      hepatectomy. This recombinant adenoviral vector has a lower toxicity than the 
      control lacZ adenovirus. This suggests that HGF may have a protective effect 
      against adenovirus-induced pathology.
FAU - Phaneuf, D
AU  - Phaneuf D
AD  - Institute for Human Gene Therapy and Department of Molecular and Cellular 
      Engineering, University of Pennsylvania, Philadelphia, USA.
FAU - Chen, S J
AU  - Chen SJ
FAU - Wilson, J M
AU  - Wilson JM
LA  - eng
GR  - P01-AD32649-05/AD/ADAMHA HHS/United States
GR  - P01-HL59407-01/HL/NHLBI NIH HHS/United States
GR  - P30-DK47757-06/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Mol Med
JT  - Molecular medicine (Cambridge, Mass.)
JID - 9501023
RN  - 0 (DNA, Recombinant)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adenoviridae/*genetics/metabolism
MH  - Animals
MH  - *Apoptosis
MH  - Cell Division
MH  - DNA/biosynthesis
MH  - DNA, Recombinant
MH  - Genetic Vectors/*administration & dosage
MH  - Hepatocyte Growth Factor/*genetics/metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Liver/*cytology/metabolism
MH  - Liver Function Tests
MH  - Liver Regeneration
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Tumor Cells, Cultured
PMC - PMC1949934
EDAT- 2000/06/20 09:00
MHDA- 2000/08/29 11:01
PMCR- 2000/02/01
CRDT- 2000/06/20 09:00
PHST- 2000/06/20 09:00 [pubmed]
PHST- 2000/08/29 11:01 [medline]
PHST- 2000/06/20 09:00 [entrez]
PHST- 2000/02/01 00:00 [pmc-release]
PST - ppublish
SO  - Mol Med. 2000 Feb;6(2):96-103.