Adenoviral gene transfer of hepatocyte growth factor prevents death of injured adult motoneurons after peripheral nerve avulsion.
Hepatocyte growth factor (HGF) exhibits strong neurotrophic activities on motoneurons both in vitro and in vivo. We examined survival-promoting effects of an adenoviral vector encoding human HGF (AxCAhHGF) on injured adult rat motoneurons after peripheral nerve avulsion. The production of HGF in COS1 cells infected with AxCAhHGF and its bioactivity were confirmed by ELISA, Western blot and Madin-Darby canine kidney (MDCK) cell scatter assay. The facial nerve or the seventh cervical segment (C7) ventral and dorsal roots of 3-month-old Fischer 344 male rats were then avulsed and removed from the stylomastoid or vertebral foramen, respectively, and AxCAhHGF, AxCALacZ (adenovirus encoding beta-galactosidase gene) or phosphate-buffered saline (PBS) was inoculated in the lesioned foramen. Treatment with AxCAhHGF after avulsion significantly prevented the loss of injured facial and C7 ventral motoneurons as compared to AxCALacZ or PBS treatment and ameliorated choline acetyltransferase immunoreactivity in these neurons. These results indicate that HGF may prevent the degeneration of motoneurons in adult humans with motoneuron injury and motor neuron diseases.
Hayashi
Yuichi
Y
Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo Metropolitan Organization for Medical Research, 2-6 Musashidai, Fuchu, Tokyo 183-8526, Japan.
Kawazoe
Yoko
Y
Sakamoto
Tsuyoshi
T
Ojima
Miyoko
M
Wang
Wei
W
Takazawa
Takanori
T
Miyazawa
Daisuke
D
Ohya
Wakana
W
Funakoshi
Hiroshi
H
Nakamura
Toshikazu
T
Watabe
Kazuhiko
K
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019556:COS Cells; D002470:Cell Survival / Q000235:genetics; D002522:Chlorocebus aethiops; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D005154:Facial Nerve / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020220:Facial Nerve Injuries / Q000503:physiopathology / Q000628:therapy*; D018014:Gene Transfer Techniques / Q000639:trends; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D008297:Male; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D009416:Nerve Regeneration / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D020127:Recovery of Function / Q000235:genetics; D016896:Treatment Outcome
D015415:Biomarkers; D017228:Hepatocyte Growth Factor; D002795:Choline O-Acetyltransferase