Hepatocyte growth factor

Hepatocyte growth factor (hepapoietin A; scatter factor)
PDB rendering based on 1bht.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1BHT, 1GMN, 1GMO, 1GP9, 1NK1, 1SHY, 1SI5, 2HGF, 2QJ2, 3HMS, 3HMT, 3HN4, 3MKP, 3SP8, 4K3J, 4O3T, 4O3U
Identifiers
Symbols	HGF ; DFNB39; F-TCF; HGFB; HPTA; SF
External IDs	OMIM: 142409 MGI: 96079 HomoloGene: 503 ChEMBL: 5479 GeneCards: HGF Gene
Gene ontology Molecular function • serine-type endopeptidase activity • protein binding • growth factor activity • serine-type peptidase activity • chemoattractant activity • identical protein binding • protein heterodimerization activity Cellular component • extracellular region • extracellular space • membrane • platelet alpha granule lumen Biological process • epithelial to mesenchymal transition • platelet degranulation • proteolysis • mitotic nuclear division • blood coagulation • positive regulation of cell proliferation • positive regulation of phosphatidylinositol 3-kinase signaling • platelet activation • hyaluronan metabolic process • positive regulation of cell migration • organ regeneration • positive regulation of myelination • cellular response to hepatocyte growth factor stimulus • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process • positive regulation of osteoblast differentiation • positive regulation of angiogenesis • positive regulation of transcription from RNA polymerase II promoter • hepatocyte growth factor receptor signaling pathway • positive regulation of peptidyl-tyrosine phosphorylation • positive chemotaxis • cell chemotaxis • regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling • positive regulation of neuron projection regeneration • negative regulation of release of cytochrome c from mitochondria • negative regulation of hydrogen peroxide-mediated programmed cell death • positive regulation of DNA biosynthetic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3082	15234
Ensembl	ENSG00000019991	ENSMUSG00000028864
UniProt	P14210	Q08048
RefSeq (mRNA)	NM_000601	NM_001289458
RefSeq (protein)	NP_000592	NP_001276387
Location (UCSC)	Chr 7: 81.7 – 81.77 Mb	Chr 5: 16.55 – 16.62 Mb
PubMed search	[1]	[2]

Hepatocyte growth factor/scatter factor (HGF/SF) is a paracrine cellular growth, motility and morphogenic factor. It is secreted by mesenchymal cells and targets and acts primarily upon epithelial cells and endothelial cells, but also acts on haemopoietic progenitor cells. It has been shown to have a major role in embryonic organ development, specifically in myogenesis, in adult organ regeneration and in wound healing.

Function

Hepatocyte growth factor regulates cell growth, cell motility, and morphogenesis by activating a tyrosine kinase signaling cascade after binding to the proto-oncogenic c-Met receptor. Hepatocyte growth factor is secreted by mesenchymal cells and acts as a multi-functional cytokine on cells of mainly epithelial origin. Its ability to stimulate mitogenesis, cell motility, and matrix invasion gives it a central role in angiogenesis, tumorogenesis, and tissue regeneration.

Structure

It is secreted as a single inactive polypeptide and is cleaved by serine proteases into a 69-kDa alpha-chain and 34-kDa beta-chain. A disulfide bond between the alpha and beta chains produces the active, heterodimeric molecule. The protein belongs to the plasminogen subfamily of S1 peptidases but has no detectable protease activity.

Clinical significance

Human HGF plasmid DNA therapy of cardiomyocytes is being examined as a potential treatment for coronary artery disease as well as treatment for the damage that occurs to the heart after myocardial infarction.

HGF may further play a role as an indicator for prognosis of chronicity for Chikungunya virus induced arthralgia. High HGF levels correlate with high rates of recovery.

Excessive local expression of HGF, along with insulin-like growth factor 1 (IGF-1) to a lesser extent, in the breasts has been associated with macromastia. HGF is also importantly involved in normal mammary gland development.

HGF has been implicated in a variety of cancers, including of the lungs, pancreas, thyroid, colon, and breast.

Circulating plasma levels

Plasma from patients with advanced heart failure presents increased levels of HGF, which correlates with a negative prognosis and a high risk of mortality. Circulating HGF has been also identified as a prognostic marker of severity in patients suffering from hypertension. Circulating HGF has been also suggested as a precocious biomarker for the acute phase of bowel inflammation.

Interactions

Hepatocyte growth factor has been shown to interact with the protein product of the C-Met oncogene, identified as the HGF receptor (HGFR). Both overexpression of the Met/HGFR receptor protein and autocrine activation of Met/HGFR by simultaneous expression of the hepatocyte growth factor ligand have been implicated in oncogenesis.

See also

• growth factor
• hepatocyte growth factor receptor (HGFR)

External links

• Hepatocyte growth factor at the US National Library of Medicine Medical Subject Headings (MeSH)
• Hepatocyte growth factor on the Atlas of Genetics and Oncology
• UCSD Signaling Gateway Molecule Page on HGF