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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
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsHepatocyte growth factor / HGF / c-Met / HLP / neurotrophic factor / neuron / Transgenic mice / neurodegenerative disease / クローニング / トランスジェニック / Sky / Gas6 / チロシンキナーゼ型受容体
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.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (69 results)

All Other

All Publications (69 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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

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

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

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Ueki, et al.: "Hypercyte factor growth gene therapy of liver cirrhosis in rats"Nature Medicine. 12. 226-230 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] F. Tamura, et al.: "FK506 promotes liver regeneration by suppressing natural killer cell activity"J. Gastroenterol. And Hepatol.. 147. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] W.Sun,H.Funakoshi,K.Matsumoto and T.Nakamura: "A sensitive quantification method for evaluating the level of HGF and c-met/HGF receptor mRNAs in the nervous system using competitive RT-PCR"Brain Res. Protocol. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [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 (1999)

    • Related Report
      1999 Annual Research Report
  • [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)

    • Related Report
      1999 Annual Research Report
  • [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 in wound healing"Lab. Invest. 79. 427-438 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Z.Jiao et al.: "Effect of D-galactosamine hydrochloride and partial hepatectomy on spontaneous hepatic injury and hepatocarcinogenesis in Long Evans Cinamon rats"Jpn. J. Cancer Res.. 90. 496-504 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.Azuma et al.: "Effect of hepatocyte growth factor on chronic rejection in rat renal allografts"Transplat. Proc.. 31. 854-855 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S.Takada et al.: "Effect of hepatocyte growth factor on tacrolimus-induced nephrotoxicity in spontaneously hypertensive rats"Transpl. Int.. 12. 27-32 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.Ueda et al.: "Gene transfection of hepatocyte growth factor attenuates reperfusion injury in the heart"Annals. Thoracic Surg.. 67. 1726-1731 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Kosai,K.Matsumoto,and T.Nakamura: "Hepatocyte growth factor prevents endotoxin-induced lethal hepatic failure in mice"Hepatology. 30. 151-159 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] R.Hasina et al.: "Autocrine and paracrine motility factors and their involvement in invasiveness in a human oral carcinoma cell line"Brit. J. Cancer. 80. 1708-1717 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Kitajima,U.Koshimizu and T.Nakamura: "Expression of a novel type of classic cadherin, PB-cadherin in developing brain and limb buds"Develop. Dyn.. 215. 206-214 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] N.Taniura-Matsumoto,K.Matsumoto and T.Nakamura: "Prostaglandin production in mouse mammary carcinoma cells confers invasive growth potential by inducing hepatocyte growth factor in fibroblasts"Brit. J. Cancer. 81. 194-202 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Kato,Y.Kato,T.Nakamura and Y.Sugiyama: "Efficient extraction by the liver governs the overall elimination of hepatocyte growth factor in rats"J. Phaemacol. Exp. Therap.. 290. 373-379 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Morishita et al.: "Therapeutic angiogenesis induced by human recombinant hepatocyte growth factor in rabbit hind limb ischemia model as a cytokine supplement therapy"Hypertention. 33. 1379-1384 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] W.G.Jiang et al.: "Hepatocyte growth factor/scatter factor decreases the expression of occuludin and transendothelial resistance (TER) and increased paracellular permeability in human vascular endothelial cells"J. Cell. Physiol.. 181. 319-329 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] C.C.Fehlner-Gardiner et al.: "Characterization of a functional relationship between hepatocyte growth factor and mouse bone marrow-derived mast cells"Differentiation. 65. 27-42 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S.Deleu et al.: "Immediate early gene expression in dog thyrocytes in response to growth proliferation and differentiation stimuli"J. Cell. Physiol.. 181. 342-354 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S.Deleu et al.: "IGF-1 or insulin, and the TSH cyclic AMP cascade separately control dog and human thyroid cell growth and DNA synthesis, and complement each other in inducing mitogenesis"Mole. Cell. Endocrin.. 149. 41-51 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S.Hayashi et al.: "Potential role of hepatocyte growth factor, a novel angiogenic growth factor in peripheral arterial disease: Downregulation of HGF in response to hypoxia in vascular cells"Circulation. 100. II-301-308 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Nagahori et al.: "Interferon-gamma upregulates the c-Met/HGF receptor expression in alvedar epithelial cells"Am. J. Respir. Cell Mol. Biol.. 21. 490-497 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] O.Amano,U.Koshimizu,T.Nakamura and S.Iseki: "Enhancement by hepatocyte growth factor (HGF) of bone and cartilage formation during embryonic mouse mandibular development in vitro"Arch. Oral Biol.,. 44. 935-946 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Nishimura et al.: "Prostate stromal cell-derived hepatocyte growth factor induces invasion of prostate cancer cells DU 145 through Tumor-stromal interaction"Prostate. 41. 145-153 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Ueki et al.: "Hepatocyte growth factor gene therapy of liver cirrhosis in rats"Nature Medicine. 5. 226-230 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] A.Uchiyama et al.: "Hepatocyte growth factor and invasion-stimulatory activity are induced in pleural fluid by surgery in lung cancer patients"Br. J. Cancer. 81. 721-726 (1999)

    • Related Report
      1999 Annual Research Report
  • [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. 34. 279-284 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Okura et al.: "Analysis of neurotrophic factor of hepatocyte growth factor (HGF) in the adult hypoglossal nerve axotomy model"Eur J. Neurosci.. 11. 4139-4144 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Sumi,K.Matsumoto,Y.Takai and T.Nakamura: "Cofilin phosphorylation and actin cytoskeletal dynamics regulated by Rho- and Cdc42-activated LIM-kinase 2"J. Cell Biol.. 147. 1519-1532 (1999)

    • Related Report
      1999 Annual Research Report
  • [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.. 13. 2186-2194 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Kawano et al.: "Phosphorylation of myosin-binding subunit (MBS) of myosin phosphatase by Rho-kinase in vivo"J. Cell Biol.. 147. 1023-1037 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] F.Tamura et al.: "FK506 promotes liver regeneration by suppressing natural killer cell activity"J. Gastroenterol. and Hepatol. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [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)

    • Related Report
      1999 Annual Research Report
  • [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)

    • Related Report
      1999 Annual Research Report
  • [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)

    • Related Report
      1999 Annual Research Report
  • [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)

    • Related Report
      1999 Annual Research Report
  • [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)

    • Related Report
      1999 Annual Research Report
  • [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)

    • Related Report
      1999 Annual Research Report
  • [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)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.Funakoshi et al.: "Targeted expression of a multifunactional chineric neurolrophin in the lesioned sciatic nerve accelerates regeneration of sensory and motor axous." Proc Natl Acad Sci USA. 95. 5269-5274 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Tahara et al.: "Hapalocyte gowth factor to recovery from alcohol-induced fatty liver in rats." J.Clin.Invest.103. 313-320 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Miyazawa et al.: " Protection of hippocampal neurons from ischemia-induced delayed neuronal death by hepatocyte growth factor:A novel neurotrophic factor." J.Celebral Blood Flow Metabolism.18. 345-348 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Ohmichi et al.: "Hepatocyle growth factor(HGF)acts as a mesenchynal-derived morphogenic factor during fetal lung develpment." Development. 125. 1315-1324 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Mizuno et al.: "Hapatocyle growth factor prevents renal fibrosis and dysfunction in a mouse model of chronio renal disease." J.Clin.Invest.101. 1827-1834 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Ueki et al.: "Hapatocyte growth factor gene therapy of liver cirrhosis in rats" Nature Medicine. 5. 226-230 (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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