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1999 Fiscal Year Final Research Report Summary

Molecular cloning and characterization of HGF family members with neurotrophic activities

Research Project

Project/Area Number 10680717
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionOsaka University

Principal Investigator

FUNAKOSHI Hiroshi  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40273685)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Toshikazu  Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (00049397)
Project Period (FY) 1998 – 1999
KeywordsHepatocyte growth factor / HGF / c-Met / HLP / neurotrophic factor / neuron / Transgenic mice / neurodegenerative disease
Research Abstract

(1) Expressional analysis of HGF and c-Met/HGF receptor in the nervous system
Expression of HGF and c-Met were examined by quantitative competitive RT-PCR and immunohitochemistry.
(a) Cerebral cortex development; both HGF and c-Met was regulated in a dynamic fashion. Taken together with in vitro activities of HGF that accelerate survival, neurite, and migration, it is suggested that HGF may have critical role for the cortical layer formation.
(b) Retinal development; both c-Met and HGF were expressed in retinal cells during development. Especially c-Met expression and in retinal neurons after eye opening and adult photoreceptor cells in adult, suggesting the activity dependent role of HGF in retina.
(2) Neurotrophic activities of HGF in vitro. Neurotrophic activities, such as survival, neurite extension, proliferation in early neuroepithelial cells and migration promoting activities in different types of neural cells were examined.
(3) Identification of HGF-like protein (HLP) as a novel neurotrophic factor. We first identify HLP as a neurotrophic factor using chicken peripheral ganglion cells.
(4) Role of HGF on motor neurodegenerative disease using transgenic approach
(a) Generation of HGF-overexpressing transgenic mice (NS-HGF-Tg) under the control of neuronal specific promoter. Generated mice were characterized.
(b) Generation and characterization of double-transgenic mice of HGF-ALS-transgenic mice. By mating HS-HGF-Tg with ALS-transgenic mice, comparing with double-transgenic mice, single-transgenic mice or sister wild-type mice.

  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] W. Sun, H. Funakoshi, K. Matsumoto and T. Nakamura: "A sensitive quantification method for evaluating the level of HGF and c-met/HGP receptor mRNAs in the nervous system using competitive RT-PCR"Brain Res. Protocol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] W. Sun, H. Funakoshi, and T. Nakamura: "Differential expression of hepatocyte growth factor and its receptor, c-Met in the rat retina during development"Brain Res.. 851. 46-53 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K. Kosai, K. Matsumoto, H. Funakoshi, and T. Nakamura: "Hepatocyte growth factor prevents endotoxin-induced lethal hepatic failure in mice"Hepatology. 30. 151-159 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] J. Wojta, et al.: "Hepatocyte growth factor increases expression of vascular endothelial growth factor and plasminogen activator inhibitor-1 in human keratinocytes and the vascular endothelial growth factor receptor flk-1 in human endothelial cells. Evidence for a paracrine loop in wound healing"Lab. Invest.. 30. 427-438 (1999)

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  • [Publications] Z. Jiao, et al.: "Effect of D-galactosamine hydrochloride and partial hepatectomy on spontaneous hepatic injury and hepatocarcinogenesis in Long Evens Cinamon rats"Jpn. J. Cancer Res.. 79. 490-504 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] H. Azuma, et al.: "Effect of hepatocyte growth factor on chronic rejection in rat renal allografts"Transplat. Proc.. 90. 854-855 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] S. Takada, et al.: "Effect of hepatocyte growth factor on tacrolimus-induced nephrotoxicity in spontaneously hypertensive rats"Transpl. Int.. 31. 27-32 (1999)

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  • [Publications] T. Ueki, et al.: "Hypercyte factor growth gene therapy of liver cirrhosis in rats"Nature Medicine. 12. 226-230 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] A. Uchiyama, et al.: "Hypercyte growth factor and invasion-stimulatory activity are induced in pleural fluid by surgery in lung cancer patients"Br. J. Cancer. 5. 721-726 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] K. Matsumoto, et al.: "Prevention of renal damage by Angiotensin II blockade, accompanied by increased renal hepatocyte growth factor in experimental hypertensive rats"Hypertension. 81. 279-284 (1999)

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  • [Publications] Y. Okura, et al.: "Analysis of neurotrophic factor of hepatocyte growth factor (HGF) in the adult hypoglossal nerve axotomy model"Eur J. Neurosci.. 34. 4139-4144 (1999)

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  • [Publications] T. Sumi, K. Matsumoto, Y. Takai and T. Nakamura: "Cofilin phosphorylation and actin cytoskeletal dynamics regulated by Rho- and Cdc42-activated LIM-kinase2"J. Cell. Biol.. 11. 1519-1532 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] M. K. Jones, et al.: "HGF triggers activation of Cox-2 gene in rat gastric epithelial cells Action mediated through the ERK2 signalling pathway"FASEB J.. 147. 2186-2194 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] Y. Kawano, et al.: "Phosphorylation of myosin-binding subunit (MBS) of myosin phosphatase by Rho-kinase in vivo"J. Cell Biol.. 13. 1023-1037 (1999)

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  • [Publications] F. Tamura, et al.: "FK506 promotes liver regeneration by suppressing natural killer cell activity"J. Gastroenterol. And Hepatol.. 147. (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] A. Uchiyama, et al: "Significance of locally-secreted hepatocyte growth factor after thoracic cancer surgery as a stimulator for postoperative cancer invasion"Jpn. J. Clin. Oncol.. (in press). (2000)

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      「研究成果報告書概要(和文)」より
  • [Publications] W. G. Jiang, et al.: "Antagonistic effect of NK4, a novel HGF variant, on in vitro angiogenesis of human vascular endothelial cells"Clin. Cancer Res.. (in press). (2000)

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      「研究成果報告書概要(和文)」より
  • [Publications] S. Hiscox, et al.: "Inhibition of HGF/SF-induced breast cancer cell matility and invasion by the HGF/SF variant, NK4"Breast Cancer Res. & Treat. (in press). (2000)

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      「研究成果報告書概要(和文)」より
  • [Publications] M. Nakano, et al.: "Hepatocyte growth factor is essential for amelioration of hyperglycemia in strepto zotocin-induced diabetic mice receiving a marginal mass of intrahepatic islet grafts"Transplantation. (in press). (2000)

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  • [Publications] T. Yamada, et al.: "Enhanced expression of hepatocyte growth factor by pulmonary ischemia reperfusion injury in the rat"Am. J. Resp. Crit. Care. Med.. (in press). (2000)

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  • [Publications] 船越 洋、中村敏一: "肝細胞増殖因子因子(HGF)の検査値と各種疾患"日本臨床. 57. 821-826 (1999)

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  • [Publications] 船越 洋、紀氏 A.優子、中村 敏一: "キメラタンパク作成法と利用."脳の科学. 21. 537-542 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sun W, Funakoshi H, Matsumoto K and Nakamura T.: "A sensitive quantification method for evaluating the level of hepatocyte growth factor (HGF) and c-met/HGF receptor mRNAs in the nervous system using competitive RT-PCR"Brain Res. Protocol. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sun W, Funakoshi H, Nakamura T.: "Differential expression of hepatocyte growth factor and its receptor, c-Met in the rat retina during development."Brain Res.. 851(1-2). 46-53 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kosai K, Matsumoto K, Funakoshi H, Nakamura T.: "Hepatocyte growth factor prevents endotoxin-induced lethal hepatic failure in mice"Hepatology. 30(1). 151-159 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Funakoshi H, Risling M, Carlstedt T, Lendahl U, Timmusk T, Metsis M, Yamamoto Y, Ibanez CF: "Targeted expression of a multifunctional chimeric neurotrophin in the Iesioned sciatic nerve accelerates regeneration of sensory and motor axons."Proc Natl Acad Sci USA. 95(9). 5269-74 (1998)

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Published: 2001-10-23  

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