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Gene Review

Hgf  -  hepatocyte growth factor

Mus musculus

Synonyms: C230052L06Rik, HGF/SF, Hepatocyte growth factor, Hepatopoietin-A, NK1, ...
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Disease relevance of Hgf


Psychiatry related information on Hgf

  • Deregulated receptor tyrosine kinase signaling, which is another important feature of human melanoma, leads to spontaneous development of metastatic melanoma after a long latency period in mice overexpressing hepatocyte growth factor/scatter factor (HGF/SF mice) [6].
  • Furthermore, with the exception of 'grooming', the effects of desipramine on behaviour of NK1-/- mice could be explained by the effects of this antidepressant on locomotor activity [7].

High impact information on Hgf

  • However, despite the availability of specific NK-1 antagonists, the function of substance P in the perception of pain remains unclear [8].
  • Thus, SF/HGF is essential for the development of several epithelial organs [9].
  • The specific ligand of the c-met protein, the motility and growth factor scatter factor/hepatocyte growth factor, is expressed in limb mesenchyme and can thus provide the signal for migration which is received by c-met [10].
  • Natural killer T (NKT) cells express a T cell receptor (TCR) and markers common to NK cells, including NK1 [11].
  • Murine CD1 has been implicated in the development and function of an unusual subset of T cells, termed natural T (NT) cells, that coexpress the T cell receptor (TCR) and the natural killer cell receptor NK1 [12].

Chemical compound and disease context of Hgf


Biological context of Hgf

  • The mouse HGF/SF cDNA was utilized for mapping Hgf to the centromeric region of mouse Chromosome 5 in apparent close proximity to the reeler mutation by the analysis of two multilocus crosses [18].
  • Hepatocyte growth factor (HGF)/Met signaling controls cell migration, growth and differentiation in several embryonic organs and is implicated in human cancer [19].
  • In NIH 3T3 cells transfected with wild-type Met, HGF inhibits apoptosis induced by serum starvation and UV irradiation [3].
  • Our data strongly suggest that SF/HGF possesses physiologically relevant scatter activity, and functions as a true morphogenetic factor by regulating migration and/or differentiation of select populations of premyogenic and neural crest cells during normal mammalian embryogenesis [2].
  • Blocking MAPK with the specific MAPK kinase inhibitor PD098059 impairs the ability of HGF to promote cell survival [3].

Anatomical context of Hgf


Associations of Hgf with chemical compounds

  • The cellular responses of SF/HGF are mediated by the c-Met tyrosine kinase receptor [9].
  • Moreover, RP 67580 displayed the profile of a specific antagonist of NK1 receptors: it was not active on NK2 and NK3 receptors as seen in binding assays and in isolated preparations of rabbit pulmonary artery and rat portal vein [23].
  • CD44 isoforms bearing heparin sulfate chains can bind to HGF/SF and facilitate its presentation to c-Met [4].
  • Specific agonists for NK-1, NK-2, and NK-3 and delta opioid receptors, carboxyterminal fragments of SP, and a variety of other peptides did not compete at the 3H-SP(1-7) binding sites, but structurally related N-terminal peptides and (D-Ala2, NMe-Phe4, Gly-ol)-enkephalin (DAMGO) were active in displacing the ligand [24].
  • It has also been shown that SF/HGF activates the protooncogene product Ras, i.e. stimulates guanine nucleotide exchange [25].

Physical interactions of Hgf


Regulatory relationships of Hgf


Other interactions of Hgf


Analytical, diagnostic and therapeutic context of Hgf


  1. Invasiveness and metastasis of NIH 3T3 cells induced by Met-hepatocyte growth factor/scatter factor autocrine stimulation. Rong, S., Segal, S., Anver, M., Resau, J.H., Vande Woude, G.F. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  2. Scatter factor/hepatocyte growth factor as a regulator of skeletal muscle and neural crest development. Takayama, H., La Rochelle, W.J., Anver, M., Bockman, D.E., Merlino, G. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  3. Anti-apoptotic signaling by hepatocyte growth factor/Met via the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways. Xiao, G.H., Jeffers, M., Bellacosa, A., Mitsuuchi, Y., Vande Woude , G.F., Testa, J.R. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  4. Hepatocyte growth factor/scatter factor induces feedback up-regulation of CD44v6 in melanoma cells through Egr-1. Recio, J.A., Merlino, G. Cancer Res. (2003) [Pubmed]
  5. Activation of Wnt/beta-catenin pathway during hepatocyte growth factor-induced hepatomegaly in mice. Apte, U., Zeng, G., Muller, P., Tan, X., Micsenyi, A., Cieply, B., Dai, C., Liu, Y., Kaestner, K.H., Monga, S.P. Hepatology (2006) [Pubmed]
  6. Rapid growth of invasive metastatic melanoma in carcinogen-treated hepatocyte growth factor/scatter factor-transgenic mice carrying an oncogenic CDK4 mutation. Tormo, D., Ferrer, A., Gaffal, E., Wenzel, J., Basner-Tschakarjan, E., Steitz, J., Heukamp, L.C., Gütgemann, I., Buettner, R., Malumbres, M., Barbacid, M., Merlino, G., Tüting, T. Am. J. Pathol. (2006) [Pubmed]
  7. A comparison of neurokinin 1 receptor knock-out (NK1-/-) and wildtype mice: exploratory behaviour and extracellular noradrenaline concentration in the cerebral cortex of anaesthetised subjects. Herpfer, I., Hunt, S.P., Stanford, S.C. Neuropharmacology (2005) [Pubmed]
  8. Altered nociception, analgesia and aggression in mice lacking the receptor for substance P. De Felipe, C., Herrero, J.F., O'Brien, J.A., Palmer, J.A., Doyle, C.A., Smith, A.J., Laird, J.M., Belmonte, C., Cervero, F., Hunt, S.P. Nature (1998) [Pubmed]
  9. Scatter factor/hepatocyte growth factor is essential for liver development. Schmidt, C., Bladt, F., Goedecke, S., Brinkmann, V., Zschiesche, W., Sharpe, M., Gherardi, E., Birchmeier, C. Nature (1995) [Pubmed]
  10. Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud. Bladt, F., Riethmacher, D., Isenmann, S., Aguzzi, A., Birchmeier, C. Nature (1995) [Pubmed]
  11. Rapid death and regeneration of NKT cells in anti-CD3epsilon- or IL-12-treated mice: a major role for bone marrow in NKT cell homeostasis. Eberl, G., MacDonald, H.R. Immunity (1998) [Pubmed]
  12. CD1d1 mutant mice are deficient in natural T cells that promptly produce IL-4. Mendiratta, S.K., Martin, W.D., Hong, S., Boesteanu, A., Joyce, S., Van Kaer, L. Immunity (1997) [Pubmed]
  13. Dynamics of beta-catenin interactions with APC protein regulate epithelial tubulogenesis. Pollack, A.L., Barth, A.I., Altschuler, Y., Nelson, W.J., Mostov, K.E. J. Cell Biol. (1997) [Pubmed]
  14. SU5416 is a potent inhibitor of hepatocyte growth factor receptor (c-Met) and blocks HGF-induced invasiveness of human HepG2 hepatoma cells. Wang, S.Y., Chen, B., Zhan, Y.Q., Xu, W.X., Li, C.Y., Yang, R.F., Zheng, H., Yue, P.B., Larsen, S.H., Sun, H.B., Yang, X. J. Hepatol. (2004) [Pubmed]
  15. Pharmacological and molecular characterization of the mechanisms involved in prostaglandin E2-induced mouse paw edema. Claudino, R.F., Kassuya, C.A., Ferreira, J., Calixto, J.B. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  16. Hepatocyte growth factor preserves beta cell mass and mitigates hyperglycemia in streptozotocin-induced diabetic mice. Dai, C., Li, Y., Yang, J., Liu, Y. J. Biol. Chem. (2003) [Pubmed]
  17. Hepatocyte growth factor gene therapy and angiotensin II blockade synergistically attenuate renal interstitial fibrosis in mice. Yang, J., Dai, C., Liu, Y. J. Am. Soc. Nephrol. (2002) [Pubmed]
  18. Structure, genetic mapping, and expression of the mouse Hgf/scatter factor gene. Lee, C.C., Kozak, C.A., Yamada, K.M. Cell Adhes. Commun. (1993) [Pubmed]
  19. Mitogen-inducible gene 6 is an endogenous inhibitor of HGF/Met-induced cell migration and neurite growth. Pante, G., Thompson, J., Lamballe, F., Iwata, T., Ferby, I., Barr, F.A., Davies, A.M., Maina, F., Klein, R. J. Cell Biol. (2005) [Pubmed]
  20. Hepatocyte growth factor/scatter factor is a motogen for interneurons migrating from the ventral to dorsal telencephalon. Powell, E.M., Mars, W.M., Levitt, P. Neuron (2001) [Pubmed]
  21. Scatter factor/hepatocyte growth factor and its receptor, the c-met tyrosine kinase, can mediate a signal exchange between mesenchyme and epithelia during mouse development. Sonnenberg, E., Meyer, D., Weidner, K.M., Birchmeier, C. J. Cell Biol. (1993) [Pubmed]
  22. A natural hepatocyte growth factor/scatter factor autocrine loop in myoblast cells and the effect of the constitutive Met kinase activation on myogenic differentiation. Anastasi, S., Giordano, S., Sthandier, O., Gambarotta, G., Maione, R., Comoglio, P., Amati, P. J. Cell Biol. (1997) [Pubmed]
  23. Pharmacological properties of a potent and selective nonpeptide substance P antagonist. Garret, C., Carruette, A., Fardin, V., Moussaoui, S., Peyronel, J.F., Blanchard, J.C., Laduron, P.M. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  24. Specific binding of substance P aminoterminal heptapeptide [SP(1-7)] to mouse brain and spinal cord membranes. Igwe, O.J., Kim, D.C., Seybold, V.S., Larson, A.A. J. Neurosci. (1990) [Pubmed]
  25. The motility signal of scatter factor/hepatocyte growth factor mediated through the receptor tyrosine kinase met requires intracellular action of Ras. Hartmann, G., Weidner, K.M., Schwarz, H., Birchmeier, W. J. Biol. Chem. (1994) [Pubmed]
  26. Alternatively spliced juxtamembrane domain of a tyrosine kinase receptor is a multifunctional regulatory site. Deletion alters cellular tyrosine phosphorylation pattern and facilitates binding of phosphatidylinositol-3-OH kinase to the hepatocyte growth factor receptor. Lee, C.C., Yamada, K.M. J. Biol. Chem. (1995) [Pubmed]
  27. Repression of Wnt-5a impairs DDR1 phosphorylation and modifies adhesion and migration of mammary cells. Jönsson, M., Andersson, T. J. Cell. Sci. (2001) [Pubmed]
  28. Hepatocyte growth factor promotes hepatocarcinogenesis through c-Met autocrine activation and enhanced angiogenesis in transgenic mice treated with diethylnitrosamine. Horiguchi, N., Takayama, H., Toyoda, M., Otsuka, T., Fukusato, T., Merlino, G., Takagi, H., Mori, M. Oncogene (2002) [Pubmed]
  29. A discoidin domain receptor 1/SHP-2 signaling complex inhibits alpha2beta1-integrin-mediated signal transducers and activators of transcription 1/3 activation and cell migration. Wang, C.Z., Su, H.W., Hsu, Y.C., Shen, M.R., Tang, M.J. Mol. Biol. Cell (2006) [Pubmed]
  30. Fibroblast growth factor-2 induces hepatocyte growth factor/scatter factor expression in osteoblasts. Blanquaert, F., Delany, A.M., Canalis, E. Endocrinology (1999) [Pubmed]
  31. Hepatocyte growth factor-mediated renal epithelial branching morphogenesis is regulated by glypican-4 expression. Karihaloo, A., Kale, S., Rosenblum, N.D., Cantley, L.G. Mol. Cell. Biol. (2004) [Pubmed]
  32. Investigation of the cooperative effects of transforming growth factor alpha and c-myc overexpression in rat liver epithelial cells. Presnell, S.C., Thompson, M.T., Strom, S.C. Mol. Carcinog. (1995) [Pubmed]
  33. Interleukin-6, hepatocyte growth factor, and their receptors in biliary epithelial cells during a type I ductular reaction in mice: interactions between the periductal inflammatory and stromal cells and the biliary epithelium. Liu, Z., Sakamoto, T., Ezure, T., Yokomuro, S., Murase, N., Michalopoulos, G., Demetris, A.J. Hepatology (1998) [Pubmed]
  34. Expression of the met receptor tyrosine kinase in muscle progenitor cells in somites and limbs is absent in Splotch mice. Yang, X.M., Vogan, K., Gros, P., Park, M. Development (1996) [Pubmed]
  35. Protective effect of hepatocyte growth factor on interferon-gamma-induced cytotoxicity in mouse hepatocytes. Morita, M., Watanabe, Y., Akaike, T. Hepatology (1995) [Pubmed]
  36. Substance P modulates antigen-induced, IFN-gamma production in murine Schistosomiasis mansoni. Blum, A.M., Metwali, A., Cook, G., Mathew, R.C., Elliott, D., Weinstock, J.V. J. Immunol. (1993) [Pubmed]
  37. Osteopontin contributes to hepatocyte growth factor-induced tumor growth and metastasis formation. Ariztia, E.V., Subbarao, V., Solt, D.B., Rademaker, A.W., Iyer, A.P., Oltvai, Z.N. Exp. Cell Res. (2003) [Pubmed]
  38. Hepatocyte Growth Factor/Scatter Factor Promotes Retinal Angiogenesis through Increased Urokinase Expression. Colombo, E.S., Menicucci, G., McGuire, P.G., Das, A. Invest. Ophthalmol. Vis. Sci. (2007) [Pubmed]
  39. Hepatocyte growth factor/scatter factor facilitates migration of GN-11 immortalized LHRH neurons. Giacobini, P., Giampietro, C., Fioretto, M., Maggi, R., Cariboni, A., Perroteau, I., Fasolo, A. Endocrinology (2002) [Pubmed]
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