Hepatocyte growth factor promotes endogenous repair and functional recovery after spinal cord injury.
Many therapeutic interventions using neurotrophic factors or pharmacological agents have focused on secondary degeneration after spinal cord injury (SCI) to reduce damaged areas and promote axonal regeneration and functional recovery. Hepatocyte growth factor (HGF), which was identified as a potent mitogen for mature hepatocytes and a mediator of inflammatory responses to tissue injury, has recently been highlighted as a potent neurotrophic and angiogenic factor in the central nervous system (CNS). In the present study, we revealed that the extent of endogenous HGF up-regulation was less than that of c-Met, an HGF receptor, during the acute phase of SCI and administered exogenous HGF into injured spinal cord using a replication-incompetent herpes simplex virous-1 (HSV-1) vector to determine whether HGF exerts beneficial effects and promotes functional recovery after SCI. This treatment resulted in the significant promotion of neuron and oligodendrocyte survival, angiogenesis, axonal regrowth, and functional recovery after SCI. These results suggest that HGF gene delivery to the injured spinal cord exerts multiple beneficial effects and enhances endogenous repair after SCI. This is the first study to demonstrate the efficacy of HGF for SCI.
Kitamura
Kazuya
K
Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, Japan.
Iwanami
Akio
A
Nakamura
Masaya
M
Yamane
Junichi
J
Watanabe
Kota
K
Suzuki
Yoshinori
Y
Miyazawa
Daisuke
D
Shibata
Shinsuke
S
Funakoshi
Hiroshi
H
Miyatake
Shinichi
S
Coffin
Robert S
RS
Nakamura
Toshikazu
T
Toyama
Yoshiaki
Y
Okano
Hideyuki
H
D000818:Animals; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage / Q000378:metabolism*; D007150:Immunohistochemistry; D007278:Injections, Spinal; D018919:Neovascularization, Physiologic; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000628:therapy*; D015854:Up-Regulation
D009414:Nerve Growth Factors; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met