Hepatocyte Growth Factor (HGF), also known as scatter factor, is a multifunctional cytokine that plays a crucial role in various biological processes, including cell growth, motility, and morphogenesis. Initially identified as a potent mitogen for hepatocytes, HGF has since been recognized for its broader biological activities.
HGF was first reported in 1984 as a potent mitogen for rat hepatocytes in primary culture . The primary structure of HGF was elucidated in 1989 through cDNA cloning, revealing it as a novel growth factor . Around the same time, scatter factor was identified from fibroblast-cultured media as a factor inducing scattering in epithelial cells. Subsequent biochemical analyses revealed that HGF and scatter factor are identical .
The HGF gene is located on chromosome 7q21.1 and comprises 18 exons and 17 introns . Mature HGF is a heterodimer composed of disulfide-linked α- and β-chains. The α-chain contains an N-terminal hairpin domain and four kringle domains, while the β-chain contains a serine proteinase homology domain . HGF is biosynthesized as an inactive single chain and is activated through cleavage by several serine proteinases .
HGF stimulates hepatocyte proliferation and acts as an anti-apoptotic factor, making it a potential therapeutic agent for treating fatal liver diseases . It also plays a role in cell motility, morphogenesis, and tissue regeneration. The HGF-Met signaling pathway is essential for various developmental and physiological processes .
Recombinant human HGF (rh-HGF) is produced using genetic engineering techniques. It is expressed in a mouse myeloma cell line (NSO) and is used in various clinical and research applications . The recombinant form retains the biological activities of natural HGF and has been evaluated for its therapeutic potential in clinical trials .
rh-HGF has been investigated for its potential in treating acute liver failure (ALF) and other liver diseases. Clinical trials have shown that rh-HGF can be administered safely, with manageable side effects such as a moderate decrease in blood pressure . Further research is needed to determine its efficacy at higher doses .