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Hepatocyte growth factor (HGF) is a protein-coding gene involved in regulation of cellular growth, homeostasis and regeneration. The HGF gene is activated by binding onto a mesenchymal epithelial transition factor (MET) receptor. When activated, this gene acts as a growth factor by promoting hepatocyte regeneration in stem and progenitor cells. HGF imbalance is associated with many types of cancer and growth deficiencies.
In terms of genetics, the protein-coding HGF gene is named hepatopoietin A/scatter factor. Previous names include deafness and autosomal recessive 39. The hepatocyte growth factor receptor (HGFR) is called c-MET. Hepatocyte growth factor is synonymous with hepatocyte growth factor/scatter factor (HGF/SF) and is often referred to as HGF/SF in scientific literature.
On a cellular level, HGF is a polypeptide excreted by mesenchymal cells that acts as a multi-functional cytokine on epithelial-originating cells. The cellular response by HGF is mediated by the c-MET tyrosine kinase receptor. A disulfide bond between the alpha and beta chains activates HGF, which binds to c-MET and triggers the tyrosine kinase signaling cascade. The end result is hepatocyte regeneration in stem cells as well as progenitor cells.
The ability to act on progenitor cells as well as stem cells has been shown to aid in embryonic organ development and adult organ regeneration. The role of HGF in paracrine cellular growth is also important for tissue regeneration, tumorigenesis and angiogenesis. Proper excretion of HGF is crucial for organogenesis of the liver and other organs.
The expression of HGF and MET directly affects the cellular growth cycle. If an insufficient level of HGF is present, growth can become stunted. The liver can become small and nearly depleted of parenchymal cells in the absence of HGF. Too much HGF can lead to tumorigenesis, meaning that, if too much HGF is present, cancerous tumors can develop.
The connection to epithelial cells gives HGF the chance to promote the expression of another growth factor, vascular epithelial growth factor (VEGF). In this way, HGF has an effect on angiogenesis. Angiogenesis is a normal part of the growth and healing process, but it also contributes to tumorigenesis when HGF is inappropriately expressed in the cells.
The association of HGF with certain types of cancer is evidenced by cases of imbalanced expression of the HGF gene in cancer patients. The connection between cancer and the HGF c-MET pathway has become a target for the development of molecular therapy.
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