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HGF family that includes HGF & HLP/MSP as a novel neurotrophic family

Research Project

Project/Area Number 14580742
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, Associate Professor, 医学系研究科, 助教授 (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) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsNeurodegenerative disease / HGF / c-Met / Neurotrophic / Amyotrophic lateral sclerosis (ALS) / Neurons / Glia / Transgenic mice / 肝細胞増殖因子(HGF) / HGF-like protein(HLP) / Ron / ミクログリア / 神経栄養因子
Research Abstract

We previously indeitified that HGF and its family member, HGF-like protein (HLP)/MSP are novel neurotrophic factors for variety of neurons, such as cerebral cortex, hippocampus, midbrain dopaminergic, sensory, motor and sympathetic neurons. In the current study, we further investigated the roles of HGF and HLP in the nervous system, especially in neurodegenerative diseases. In addition, by generation and analyses of LIMK-2 KO mice, we found that LIM-kinase 2 play an important role in neuronal degenerative process.
(1) Roles of HGF in amyotrophic lateral sclerosis (ALS): Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive loss of motoneurons and degeneration of motor axons. We showed that overexpression of hepatocyte growth factor (HGF) in the nervous system attenuates motoneuron death and axonal degeneration and prolongs the life span of transgenic mice overexpressing mutated SOD1. HGF prevented induction of caspase-1 in motoneurons an … More d retained the levels of the glial-specific glutamate transporter (EAAT2/GLT1) in reactive astrocytes. We propose that HGF may be the first example of an endogenous growth factor that can alleviate the symptoms of ALS by direct neurotrophic activities on motoneurons and indirect activities on glial cells, presumably favoring a reduction in glutamatergic neurotoxicity.
(2) Roles of HLP/MSP in the nervous system: We previously reported that HLP act as a novel neurotrophic factor for chicken sensory neurons. Here we identified that Ron/HLP receptor is expressed in primary microglia and HLP accelerates microglial activities in vitro. Taken together with notion that HLP is neurotrophic, HLP may be one of the critical factor involving not only the protecting process of the neurodegeneration but also the degeneration and regeneration processes of the nervous system.
(3) Roles of LIMKase-2 (LIMK2) in the nervous system: By generation and analyses if LIMK2 deficient mice, we found that limk2 variants were differently expressed in hippocampal neurons and play important roles in neurodegenerative process of hippocampal neurons. Less

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (38 results)

All Other

All Publications (38 results)

  • [Publications] H.Funakoshi, T.Nakamura: "Hepatocyte growth factor : from diagnosis to clinical applications."Clinica Chimica Acta. 327(1-2). 1-23 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Kato, H.Funakoshi, et al.: "Expression of hepatocyte growth factor and c-Met in the anterior horn cells of the spinal cord in the patients with amyotrophic lateral sclerosis (ALS): immunohistochemical studies on sporadic ALS and familial ALS with superoxide dismutase 1 gene mutation."Acta Neuropathol. 106(2). 112-120 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Takahashi, H.Funakoshi, T.Nakamura: "LIM-kinase as a regulator of actin dynamics in spermatogenesis."Cytogenic and Genome Research. (印刷中). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Koike, T.Nakamura, et al.: "Enhanced angiogenesis and improvement of neuropathy by cotransfection of human hepatocyte growth factor and prostacyclin synthase gene."FASEB J.. 17(6). 779-781 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Oshima, T.Nakamura, et al.: "Intrathecal injection of HVJ-E containing HGF gene to cerebrospinal fluid can prevent and ameliorate hearing impairment in rats."FASEB J.. 18(1). 212-214 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Funakoshi H, Yonemasu T, et al.: "Identification of Gas6, a putative ligand for Sky and Axl receptor tyrosine kinases, as a novel neurotrophic factor for hippocampal neurons."J Neurosci Res.. 68(2). 150-160 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sun W, Funakoshi H, et al.: "Overexpression of HGF retards disease progression and prolongs life span in a transgenic mouse model of ALS."J.Neurosci. 22(15). 6537-6548 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sun W, Funakoshi H, et al.: "Localization and functional role of hepatocyte growth factor (HGGF) and its receptor c-met in the rat developing cerebral cortex."Mol Brain Res.. 103(1-2). 36-48 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kishi YA, Funakoshi H, et al.: "Molecular cloning, expression and partial characterization of Xksy, Xen opus member of the Sky family of receptor tyrosine kinases."Gene. 288(1-2). 29-40 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 船越 洋, 中村 敏一: "神経栄養因子による神経難病治療の可能性"現代医療. 34(1). 245-259 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 中村 健二, 船越 洋, 中村 敏一: "神経再生因子としての肝細胞増殖因子(HGF)"脳の科学. 増刊号. 108-115 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 船越 洋, 中村 敏一: "ALSと神経栄養因子:HGFによる新しい神経栄養因子HGFによる新しい治療法開発の可能性"脳と神経. 55(10). 841-845 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 船越 洋, 中村 敏一: "神経栄養因子による神経難病治療の可能性"現代医療. 34(1). 245-259 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Funakoshi H, Nakamura T.: "Hepatocyte growth factor: from diagnosis to clinical applications."Clin Chim Acta. 327(1-2). 1-23 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takahashi H, Funakoshi H, Nakamura T.: "LIM-kinase as a regulator of actin dynamics in spermatogenesis."Cytogenet Genome Res. 103(3-4). 290-298 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kato S, Funakoshi H, Nakamura T, Kato M, Nakano I, Hirano A, Ohama E.: "Expression of hepatocyte growth factor and c-Met in the anterior horn cells of the spinal cord in the patients, with amyotrophic lateral sclerosis (ALS): immunohistochemical studies on sporadic ALS and familial ALS with superoxide dismutase 1 gene mutation."Acta Neuropathol (Befl). 106(2). 112-120 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Funakoshi H, Yonemasu T, Nakano T, Matumoto K, Nakamura T.: "Identification of Gas6, a putative ligand for Sky and Axl receptor tyrosine kinases, as a novel neurotrophic factor for hippocampal neurons."J Neurosci Res. 68(2). 150-156 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sun W, Funakoshi, H, Nakamura T.: "Overexpression of HGF retards disease progression and prolongs life span in a transgenic mouse model of ALS."J Neurosci. 22(15). 6537-6548 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sun W, Funakoshi H, Nakamura T.: "Localization and functional role of hepatocyte growth factor (HGF) and its receptor c-met in the rat developing cerebral cortex."Brain; Res.Mol Brain Res. 103(1-2). 36-48 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kishi YA, Funakoshi H, Matsumoto K, Nakamura T.: "Molecular cloning, expression and partial characterization of Xksy, Xenopus member of the Sky family of receptor tyrosine kinases."Gene. 288(1-2). 29-40 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Funakoshi, T.Nakamura: "Hepatocyte growth factor : from diagnosis to clinical applications"Clinica Chimica Acta. 327(1-2). 1-23 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] S.Kato, H.Funakoshi et al.: "Expression of hepatocyte growth factor and c-Met in the anterior horn cells of the spinal cord in the patients with amyotrophic lateral sclerosis (ALS) : immunohistochemical studies on sporadic ALS and familial ALS with superoxide dismutase 1 gene mutation"Acta Neuropathol. 106(2). 112-120 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.Takahashi, H.Funakoshi, T.Nakamura: "LIM-kinase as a regulator of actin dynamics in spermatogenesis"Cytogenic and Genome Research. (印刷中). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.Koike, T.Nakamura et al.: "Enhanced angiogenesis and improvement of neuropathy by cotransfection of human hepatocyte growth factor and prostacyclin synthase gene"FASEB J.. 17(6). 779-781 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Oshima, T.Nakamura et al.: "Intrathecal injection of HVJ-E containing HGF gene to cerebrospinal fluid can prevent and ameliorate hearing impairment in rats"FASEB J.. 18(1). 212-214 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 中村 健二, 船越 洋, 中村 敏一: "神経再生因子としての肝細胞増殖因子(HGF)"脳の科学 増刊号(神経の再生). 25巻. 108-115 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 船越 洋, 中村 敏一: "ALSと神経栄養因子:HGFによる新しい神経栄養因子HGFによる新しい治療法開発の可能性"脳と神経. 55巻10号. 841-845 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 船越 洋, 中村 敏一: "神経再生因子としての肝細胞増殖因子(HGF)"脳の科学. 増刊号(神経の再生). 533-540 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Funakoshi H, Nakamura T.: "Hepatocyte growth factor : from diagnosis to clinical applications"Clin Chim Acta. 327. 1-23 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sun W, Funakoshi H, Nakamura T: "Overexpression of HGF retards disease progression and prolongs life span in a transgenic mouse model of ALS"J. Neurosci.. 22. 6537-6548 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sun W, Funakoshi H, Nakamura T: "Localization and functional role of hepatocyte growth factor (HGF) and its receptor c-met in the rat developing cerebral cortex"Mol. Brain Res.. 103. 36-48 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Funakoshi H, Yonemasu T, Nakano T, et al.: "Identification of Gas6, a putative ligand for Sky and Axl receptor tyrosine kinases, as a novel neurotrophic factor for hippocampal neurons"J. Neurosci Res.. 68(2). 150-160 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kishi Y, Funakoshi H, Matsumoto K, Nakamura T: "Molecular cloning, expression and partial characterization of Xksy, Xenopus member of the Sky family of receptor tyrosine kinases"Gene. 288. 29-40 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 中村 健二, 船越 洋, 中村 敏一: "神経再生因子としての肝細胞増殖因子(HGF)"脳の科学. 増刊号/神経の再生. 108-115 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 船越 洋, 中村 敏一: "神経栄養因子による神経難病治療の可能性"現代医療. Vol.34.No.1. 245-253 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshimura S, Morishita R, Hayashi K, Kokuzawa J, et al.: "Gene transfer of hepatocyte growth factor to subarachnoid space in cerebral hypoperfusion model"Hypertension. 39(5). 1028-1034 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shibuki H, Katai N, Kuriowa S, Kurokawa T, Arai J, et al.: "Expression and neuroprotective effect of hepatocyte growth factor in retinal ischemia-reperfusion injury"Invest Ophthalmol Vis Sci.. 43(2). 528-536 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Koike H, Morishita R, Iguchi S, Aoki M, Matsumoto K, Nakamura: "Enhanced angiogenesis and improvement of neuropathy by cotransfection of human hepatocyte growth factor and prostacyclin"FASEB J.. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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