Recombinant Human HGF Protein

HGF, also known as scatter factor and hepatopoietin A, is a pleiotropic protein in the plasminogen subfamily of S1 peptidases. It is a multidomain molecule that includes an N-terminal PAN/APPLE‑like domain, four Kringle domains, and a serine proteinase-like domain that has no detectable protease activity (1‑5). Human HGF is secreted as an inactive 728 amino acid (aa) single chain propeptide. It is cleaved after the fourth Kringle domain by a serine protease to form bioactive
disulfide‑linked HGF with a 60 kDa alpha and 30 kDa beta chain. Alternate splicing generates human HGF isoforms that lack the proteinase‑like domain and different numbers of the Kringle domains. Human HGF shares 91%‑94% aa sequence identity with bovine, canine, feline, mouse, and rat HGF. HGF binds heparan-sulfate proteoglycans and the widely expressed receptor tyrosine kinase, HGF R/c-MET (6, 7). HGF-dependent c-MET activation is implicated in the development of many human cancers (8). HGF regulates epithelial morphogenesis by inducing cell scattering and branching tubulogenesis (9, 10). HGF induces the up‑regulation of integrin alpha2 beta1 in epithelial cells by a selective increase in alpha2 gene transcription (11). This integrin serves as a collagen I receptor, and its blockade disrupts epithelial cell branching tubulogenesis (11, 12). HGF can also alter epithelium morphology by the induction of nectin‑1 alpha ectodomain shedding, an adhesion protein component of adherens junctions (13). In the thyroid, HGF induces the proliferation, motility, and loss of differentiation markers of thyrocytes and inhibits TSH‑stimulated iodine uptake (14). HGF promotes the motility of cardiac stem cells in damaged myocardium (15).