HGFs

HGFs stands for hepatocyte growth factors, a group of secreted signaling proteins that regulate cell growth, movement, and morphogenesis in various tissues. The principal member is hepatocyte growth factor (HGF), also known as scatter factor (SF), which acts on cells expressing the MET receptor.

Source and activation: HGFs are produced by mesenchymal and other supportive cells and are typically secreted as an inactive single-chain polypeptide. Proteolytic processing activates them into a two-chain, heterodimeric form composed of an alpha and a beta chain that can bind and activate the MET receptor.

Receptor and signaling: HGF binds to the MET receptor tyrosine kinase on target cells, inducing receptor dimerization and autophosphorylation. This triggers multiple signaling cascades, notably the Ras–MAPK, PI3K–Akt, and sometimes STAT pathways. The resulting cellular responses include proliferation, survival, enhanced motility, and morphogenesis, as well as organ- and tissue-specific effects such as branching morphogenesis in epithelium.

Biological roles: HGF/MET signaling is vital for liver development and regeneration and plays a role in the development and repair of several organs, including the lung, kidney, and placenta. It also influences angiogenesis and wound healing and can modulate immune cell migration and tissue remodeling.

Clinical significance: Dysregulation of the HGF/MET axis is associated with cancer progression and metastasis in various tissues, making MET inhibitors and HGF antagonists targets of therapeutic research. Recombinant HGF has been explored in preclinical studies for tissue repair and regenerative medicine, though clinical applications remain under investigation.

See also: MET receptor, scatter factor, hepatocyte growth factor activator.