Hepatocyte growth factor
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| Location (UCSC) | Chr 7: 81.7 – 81.77 Mb | Chr 5: 16.76 – 16.83 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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Hepatocyte growth factor (HGF) or scatter factor (SF) is a
endothelial cells, but also acts on haemopoietic progenitor cells and T 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.[5]
Function
Hepatocyte growth factor regulates cell growth, cell motility, and
tumorogenesis, and tissue regeneration.[9]
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
Clinical significance
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.[10][11]
As well as the well-characterised effects of HGF on endothelial cells and haemopoietic progenitor cells, HGF also regulates the chemotaxis of T cells into heart tissue. Binding of HGF by c-Met, expressed on T cells, causes the upregulation of c-Met, CXCR3, and CCR4 which in turn imbues them with the ability to migrate into heart tissue.[12] HGF also promotes angiogenesis in ischemia injury.[13]
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.[14]
Excessive local expression of HGF in the
HGF has been implicated in a variety of cancers, including of the lungs, pancreas, thyroid, colon, and breast.[18][19][20]
Increased expression of HGF has been associated with the enhanced and scarless wound healing capabilities of fibroblast cells isolated from the oral mucosa tissue.[21]
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.[22][23] Circulating HGF has been also identified as a prognostic marker of severity in patients with hypertension.[24] Circulating HGF has been also suggested as a precocious biomarker for the acute phase of bowel inflammation.[25]
Pharmacokinetics
intravenous injection is cleared rapidly from circulation by the liver, with a half-life of approximately 4 minutes.[26][27][28][29]
Modulators
small-molecule compound that directly binds to HGF and potentiates its ability to activate its receptor, c-Met.[30] It is a strong inducer of neurogenesis and is being studied for the potential treatment of Alzheimer's disease and Parkinson's disease.[31][32]
Interactions
Hepatocyte growth factor has been shown to
autocrine activation of Met/HGFR by simultaneous expression of the hepatocyte growth factor ligand have been implicated in oncogenesis.[35][36]
Hepatocyte growth factor interacts with the sulfated glycosaminoglycans heparan sulfate and dermatan sulfate.[37][38] The interaction with heparan sulfate allows hepatocyte growth factor to form a complex with c-Met that is able to transduce intracellular signals leading to cell division and cell migration.[37][39]
See also
- Epidermal growth factor
- Insulin-like growth factor 1
- Epithelial–mesenchymal transition
- Madin-Darby Canine Kidney Cells
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000019991 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028864 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Gallagher, J.T., Lyon, M. (2000). "Molecular structure of Heparan Sulfate and interactions with growth factors and morphogens". In Iozzo, M, V. (ed.). Proteoglycans: structure, biology and molecular interactions. Marcel Dekker Inc. New York, New York. pp. 27–59.
{{cite book}}: CS1 maint: multiple names: authors list (link) - ^ PMID 1846706.
- PMID 8514254.
- PMID 35909816.
- ^ a b "Entrez Gene: HGF hepatocyte growth factor (hepapoietin A; scatter factor)".
- S2CID 23419866.
- S2CID 26812780.
- PMID 26070483.
- PMID 27434585.
- PMID 21288813.
- PMID 24720804.
- PMID 7555716.
- S2CID 9310133.
- ISBN 978-1-4612-1876-0.
- S2CID 3089594.
- PMID 21934211.
- PMID 28837064.
- PMID 23218577.
- S2CID 22426278.
- S2CID 6615179.
- PMID 25174881.
- PMID 11283849.
- PMID 8450646.
- S2CID 20021569.
- PMID 17519892.
- PMID 25187433.
- PMID 25649658.
- S2CID 41360989.
- PMID 8380735.
- PMID 1655405.
- PMID 7553606.
- PMID 8930021.
- ^ S2CID 29982976.
- S2CID 39689713.
- S2CID 25507615.
Further reading
- Michalopoulos GK, Zarnegar R (1992). "Hepatocyte Growth Factor". Hepatology. 15 (1): 149–54. S2CID 39873193.
- Nakamura T (1992). "Structure and function of hepatocyte growth factor". Progress in Growth Factor Research. 3 (1): 67–85. PMID 1838014.
- Ware LB, Matthay MA (May 2002). "Keratinocyte and hepatocyte growth factors in the lung: roles in lung development, inflammation, and repair". American Journal of Physiology. Lung Cellular and Molecular Physiology. 282 (5): L924-40. S2CID 22175256.
- Funakoshi H, Nakamura T (January 2003). "Hepatocyte growth factor: from diagnosis to clinical applications". Clinica Chimica Acta; International Journal of Clinical Chemistry. 327 (1–2): 1–23. PMID 12482615.
- Skibinski G (2004). "The role of hepatocyte growth factor/c-met interactions in the immune system". Archivum Immunologiae et Therapiae Experimentalis. 51 (5): 277–82. PMID 14626426.
- Kalluri R, Neilson EG (December 2003). "Epithelial-mesenchymal transition and its implications for fibrosis". The Journal of Clinical Investigation. 112 (12): 1776–84. PMID 14679171.
- Hurle RA, Davies G, Parr C, Mason MD, Jenkins SA, Kynaston HG, Jiang WG (October 2005). "Hepatocyte growth factor/scatter factor and prostate cancer: a review". Histology and Histopathology. 20 (4): 1339–49. PMID 16136515.
- Kemp LE, Mulloy B, Gherardi E (June 2006). "Signalling by HGF/SF and Met: the role of heparan sulphate co-receptors". Biochemical Society Transactions. 34 (Pt 3): 414–7. S2CID 31340761.
- Ejaz A, Epperly MW, Hou W, Greenberger JS, Rubin PJ (March 2019). "Adipose-derived stem cell therapy ameliorates ionizing irradiation fibrosis (RIF) via hepatocyte growth factor mediated TGF-β down regulation and recruitment of bone marrow cells". Stem Cells. 37 (6): 791–802. PMID 30861238.
External links
- Hepatocyte+growth+factor at the U.S. 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
- Overview of all the structural information available in the PDB for UniProt: P14210 (Hepatocyte growth factor) at the PDBe-KB.
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