title: Hepatocyte growth factor twenty years on: Much more than a growth factor.
abstract: Liver regeneration depends on the proliferation of mature hepatocytes. In the 1980s, the method for the cultivation of mature hepatocytes provided an opportunity for the discovery of hepatocyte growth factor (HGF) as a protein that is structurally and functionally different from other growth factors. In 1991, the scatter factor, tumor cytotoxic factor, and 3-D epithelial morphogen were identified as HGF, and Met tyrosine kinase was identified as the receptor for HGF. Thus, the connection of apparently unrelated research projects rapidly enriched the research on HGF in different fields. The HGF-Met pathway plays important roles in the embryonic development of the liver and the placenta, in the migration of myogenic precursor cells, and in epithelial morphogenesis. The use of tissue-specific knockout mice demonstrated that in mature tissues the HGF-Met pathway plays a critical role in tissue protection and regeneration, and in providing less susceptibility to chronic inflammation and fibrosis. In various injury and disease models, HGF promotes cell survival, regeneration of tissues, and suppresses and improves chronic inflammation and fibrosis. Drug development using HGF has been challenging, but extensive preclinical studies to address its therapeutic effects have provided significant results sufficient for the development of HGF as a biological drug in the regeneration-based therapy of diseases. Clinical trials using recombinant human HGF protein, or HGF genes, are in progress for the treatment of diseases.
authors.affiliation: Cancer Research Institute, Kanazawa University, Kakuma-machi, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Katsuya
authors.initials: K
authors.lastname: Sakai
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Kunio
authors.initials: K
authors.lastname: Matsumoto
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental; D017228:Hepatocyte Growth Factor / Q000737:chemistry / Q000235:genetics / Q000266:history / Q000378:metabolism* / Q000627:therapeutic use; D022781:Hepatocytes / Q000378:metabolism; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D008099:Liver / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D008115:Liver Regeneration; D008958:Models, Molecular; D009024:Morphogenesis; D038081:Organogenesis; D011487:Protein Conformation; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met