Disease relevance of Hgf

• Invasiveness and metastasis of NIH 3T3 cells induced by Met-hepatocyte growth factor/scatter factor autocrine stimulation [1].
• Here we provide functional evidence that inappropriate expression of SF/HGF in transgenic mice influences the development of two distinct migratory cell lineages, resulting in ectopic skeletal muscle formation and melanosis in the central nervous system, and patterned hyperpigmentation of the skin [2].
• In experiments with human SK-LMS-1 leiomyosarcoma cells, we show that the Akt kinase is activated by HGF in a time- and dose-dependent manner by phosphatidylinositol 3-kinase (PI3-kinase) [3].
• Hepatocyte growth factor/scatter factor induces feedback up-regulation of CD44v6 in melanoma cells through Egr-1 [4].
• It is also known that delivery of the human HGF gene cloned in a plasmid under a CMV promoter results in hepatomegaly in mice [5].

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

• Similar HGF/SF treatment of cysts derived from cells expressing NH2-terminal deleted beta-catenins resulted in cells that proliferated but formed cell aggregates (polyps) within the cyst rather than tubules [13].
• CONCLUSIONS: Inhibition of various solid tumors growth and metastasis by SU5416 may be partially attributed to blocking activation of the hepatocyte growth factor receptor [14].
• Conversely, the selective NK2, NK3, and calcitonin gene-related peptide (CGRP) CGRP(8-37) receptor antagonists all failed to interfere with PGE2-induced paw edema [15].
• Hepatocyte growth factor preserves beta cell mass and mitigates hyperglycemia in streptozotocin-induced diabetic mice [16].
• Hepatocyte growth factor gene therapy and angiotensin II blockade synergistically attenuate renal interstitial fibrosis in mice [17].

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

• The spatial patterns of migratory interneurons reflect the complementary expression of hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, MET, in the forebrain [20].
• Hepatocyte growth factor/scatter factor is a motogen for interneurons migrating from the ventral to dorsal telencephalon [20].
• 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 [21].
• A natural hepatocyte growth factor/scatter factor autocrine loop in myoblast cells and the effect of the constitutive Met kinase activation on myogenic differentiation [22].
• Scatter factor/hepatocyte growth factor as a regulator of skeletal muscle and neural crest development [2].

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

• 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 [26].
• We found that overexpression of Wnt-5a protein enhanced cell-to-collagen binding and abolished hepatocyte growth factor-stimulated migration of HB2 transfectants through collagen matrices [27].

Regulatory relationships of Hgf

• Hepatocyte growth factor promotes hepatocarcinogenesis through c-Met autocrine activation and enhanced angiogenesis in transgenic mice treated with diethylnitrosamine [28].
• Mutation of tyrosine 703 or 796 of DDR1 abolished the ability of DDR1 to inhibit the tyrosine phosphorylation of Stat1 and Stat3 and restored collagen-induced cell migration and hepatocyte growth factor-induced branching tubulogenesis in collagen gel [29].
• Fibroblast growth factor-2 induces hepatocyte growth factor/scatter factor expression in osteoblasts [30].
• Hepatocyte growth factor-mediated renal epithelial branching morphogenesis is regulated by glypican-4 expression [31].
• Our data suggest that the overexpression of TGF-alpha leads to enhanced responsiveness to hepatocyte growth factor, whereas the concomitant overexpression of c-myc confers growth-factor independence, providing a potential explanation of the mechanisms by which the overexpression of these genes results in transformation [32].

Other interactions of Hgf

• The interleukin-6 (IL-6)/gp-80 and hepatocyte growth factor (HGF)/met ligand/receptor systems have been shown to stimulate biliary epithelial cell (BEC) DNA synthesis in vitro [33].
• Significantly, no met-expressing cells were observed in the limbs of homozygous Splotch-2H and Splotch-delayed animals, whereas HGF/SF expression was not affected [34].
• Protective effect of hepatocyte growth factor on interferon-gamma-induced cytotoxicity in mouse hepatocytes [35].
• There are three distinct tachykinin receptors, called NK-1, NK-2 and NK-3 [36].
• Osteopontin contributes to hepatocyte growth factor-induced tumor growth and metastasis formation [37].

Analytical, diagnostic and therapeutic context of Hgf

• We sought to determine the role of HGF/Met in apoptosis and identify signal transducers involved in this process [3].
• In conclusion, beta-catenin- and HGF-mediated signaling pathways cooperate in hepatocyte proliferation, which may be crucial in liver development, regeneration following partial hepatectomy, and pathogenesis of hepatocellular carcinoma [5].
• To investigate a possible role for HGF/SF and its receptor, the Met tyrosine kinase, in embryonic development, we have analyzed their expression in mouse embryos from day 7.5 of gestation by whole-mount in situ hybridization [34].
• PURPOSE: The purpose of this study was to determine the role of hepatocyte growth factor (HGF) and c-Met in the initiation and development of retinal neovascularization and to determine whether inhibition of this system can suppress the extent of angiogenesis in an animal model [38].
• In addition, HGF/SF treatment promotes specific migratory activity of GN11 cells, as demonstrated by collagen gel assay, time-lapse video microscopy, and Boyden's chamber experiments [39].

References