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2014 ; 2
(4
): 275-300
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HGF-Met Pathway in Regeneration and Drug Discovery
#MMPMID28548072
Matsumoto K
; Funakoshi H
; Takahashi H
; Sakai K
Biomedicines
2014[Oct]; 2
(4
): 275-300
PMID28548072
show ga
Hepatocyte growth factor (HGF) is composed of an ?-chain and a ?-chain, and these
chains contain four kringle domains and a serine protease-like structure,
respectively. Activation of the HGF-Met pathway evokes dynamic biological
responses that support morphogenesis (e.g., epithelial tubulogenesis),
regeneration, and the survival of cells and tissues. Characterizations of
conditional Met knockout mice have indicated that the HGF-Met pathway plays
important roles in regeneration, protection, and homeostasis in various cells and
tissues, which includes hepatocytes, renal tubular cells, and neurons.
Preclinical studies designed to address the therapeutic significance of HGF have
been performed on injury/disease models, including acute tissue injury, chronic
fibrosis, and cardiovascular and neurodegenerative diseases. The promotion of
cell growth, survival, migration, and morphogenesis that is associated with
extracellular matrix proteolysis are the biological activities that underlie the
therapeutic actions of HGF. Recombinant HGF protein and the expression vectors
for HGF are biological drug candidates for the treatment of patients with
diseases and injuries that are associated with impaired tissue function. The
intravenous/systemic administration of recombinant HGF protein has been well
tolerated in phase I/II clinical trials. The phase-I and phase-I/II clinical
trials of the intrathecal administration of HGF protein for the treatment of
patients with amyotrophic lateral sclerosis and spinal cord injury, respectively,
are ongoing.
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