Hepatocyte growth factor

Hepatocyte growth factor (hepapoietin A; scatter factor)

PDB rendering based on 1bht.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsHGF ; DFNB39; F-TCF; HGFB; HPTA; SF
External IDsOMIM: 142409 MGI: 96079 HomoloGene: 503 ChEMBL: 5479 GeneCards: HGF Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez308215234
EnsemblENSG00000019991ENSMUSG00000028864
UniProtP14210Q08048
RefSeq (mRNA)NM_000601NM_001289458
RefSeq (protein)NP_000592NP_001276387
Location (UCSC)Chr 7:
81.33 – 81.4 Mb		Chr 5:
16.55 – 16.62 Mb
PubMed search

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.[1]

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.[2] 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.[3]

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.[3]

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.[4][5]

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.[6]

Interactions

Hepatocyte growth factor has been shown to interact with C-Met.[2][7][8]

See also

References

  1. ↑ Gallagher, J.T., Lyon, M. (2000). "Molecular structure of Heparan Sulfate and interactions with growth factors and morphogens". In Iozzo, M, V. Proteoglycans: structure, biology and molecular interactions. Marcel Dekker Inc. New York, New York. pp. 27–59.
  2. ↑ 2.0 2.1 Bottaro DP, Rubin JS, Faletto DL, Chan AM, Kmiecik TE, Vande Woude GF, Aaronson SA (February 1991). "Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product". Science 251 (4995): 802–4. doi:10.1126/science.1846706. PMID 1846706.
  3. ↑ 3.0 3.1 "Entrez Gene: HGF hepatocyte growth factor (hepapoietin A; scatter factor)".
  4. ↑ Yang, Z. J.; Zhang, Y. R.; Chen, B.; Zhang, S. L.; Jia, E. Z.; Wang, L. S.; Zhu, T. B.; Li, C. J.; Wang, H.; Huang, J.; Cao, K. J.; Ma, W. Z.; Wu, B.; Wang, L. S.; Wu, C. T. (2008). "Phase I clinical trial on intracoronary administration of Ad-hHGF treating severe coronary artery disease". Molecular Biology Reports 36 (6): 1323–1329. doi:10.1007/s11033-008-9315-3. PMID 18649012.
  5. ↑ Hahn, W.; Pyun, W. B.; Kim, D. S.; Yoo, W. S.; Lee, S. D.; Won, J. H.; Shin, G. J.; Kim, J. M.; Kim, S. (2011). "Enhanced cardioprotective effects by coexpression of two isoforms of hepatocyte growth factor from naked plasmid DNA in a rat ischemic heart disease model". The Journal of Gene Medicine 13 (10): 549–555. doi:10.1002/jgm.1603. PMID 21898720.
  6. ↑ Chow A, Her Z, Ong EK, Chen JM, Dimatatac F, Kwek DJ, Barkham T, Yang H, Rénia L, Leo YS, Ng LF (January 2011). "Persistent arthralgia induced by Chikungunya virus infection is associated with interleukin-6 and granulocyte macrophage colony-stimulating factor". J. Infect. Dis. 203 (2): 149–57. doi:10.1093/infdis/jiq042. PMC 3071069. PMID 21288813.
  7. ↑ Comoglio PM (1993). "Structure, biosynthesis and biochemical properties of the HGF receptor in normal and malignant cells". EXS 65: 131–65. PMID 8380735.
  8. ↑ Naldini L, Weidner KM, Vigna E, Gaudino G, Bardelli A, Ponzetto C, Narsimhan RP, Hartmann G, Zarnegar R, Michalopoulos GK (October 1991). "Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor". EMBO J. 10 (10): 2867–78. PMC 452997. PMID 1655405.

Further reading

  • Michalopoulos GK, Zarnegar R (1992). "Hepatocyte Growth Factor". Hepatology 15 (1): 149–54. doi:10.1002/hep.1840150125.
  • Nakamura T (1992). "Structure and function of hepatocyte growth factor". Prog. Growth Factor Res. 3 (1): 67–85. doi:10.1016/0955-2235(91)90014-U. PMID 1838014.
  • Ware LB, Matthay MA (2002). "Keratinocyte and hepatocyte growth factors in the lung: roles in lung development, inflammation, and repair". Am. J. Physiol. Lung Cell Mol. Physiol. 282 (5): L924–40. doi:10.1152/ajplung.00439.2001. PMID 11943656.
  • Funakoshi H, Nakamura T (2003). "Hepatocyte growth factor: from diagnosis to clinical applications". Clin. Chim. Acta 327 (1–2): 1–23. doi:10.1016/S0009-8981(02)00302-9. PMID 12482615.
  • Skibinski G (2004). "The role of hepatocyte growth factor/c-met interactions in the immune system". Arch. Immunol. Ther. Exp. (Warsz.) 51 (5): 277–82. PMID 14626426.
  • Kalluri R, Neilson EG (2004). "Epithelial-mesenchymal transition and its implications for fibrosis". J. Clin. Invest. 112 (12): 1776–84. doi:10.1172/JCI20530. PMC 297008. PMID 14679171.
  • Hurle RA; Davies G; Parr C et al. (2006). "Hepatocyte growth factor/scatter factor and prostate cancer: a review". Histol. Histopathol. 20 (4): 1339–49. PMID 16136515.
  • Kemp LE, Mulloy B, Gherardi E (2006). "Signalling by HGF/SF and Met: the role of heparan sulphate co-receptors". Biochem. Soc. Trans. 34 (Pt 3): 414–7. doi:10.1042/BST0340414. PMID 16709175.

External links