1994 Fiscal Year Annual Research Report

HGFによる脳神経系の生存維持とHGFからみた神経変性疾患の病態解析

Research Project

Project/Area Number	06272221
Research Institution	Osaka University
Principal Investigator	松本邦夫大阪大学, 医学部, 講師 (90201780)
Keywords	HGF / c-met / 神経栄養因子 / 脳傷害
Research Abstract	HGFは細胞増殖の促進に加え、細胞運動性促進、上皮形態形成の誘導など多様な生理活性を有する増殖因子である。また、HGFは肝臓をはじめ、腎臓、肺などの器官の再生を促す器官再生因子としての機能を有している。本研究においては、1)脳におけるHGFならびにc-metレセプターの発現、2)培養神経細胞に対するin vitroでのHGFの作用、3)脳傷害に伴うHGFならびにそのレセプターの発現について解析した。成熟ラット脳においてHGF、c-met/HGFレセプターmRNAは脳内の多くの領域に発現されており、in situ hybridizationによりHGF mRNAは大脳皮質、海馬、そして扁桃体において発現が認められた。また、これらの領域においてHGF蛋白はニューロンに存在していることを免疫組織染色法を用いて確認した。さらに、HGF特異染色は帯状束、小脳、橋、延髄においてグリア細胞にも認められた。一方、c-met/HGFレセプターmRNAは嗅球、大脳皮質、一次嗅覚皮質、海馬、小脳に局在が認められた。ラット胎児海馬由来神経細胞の初代培養系にHGFを加え培養したところHGFは初代培養神経細胞の生存を促進した。さらに、成熟ラットの大脳に一過性の脳虚血障害を施すと、虚血傷害に応じてHGFならびにc-met/HGFレセプターの顕著な発現誘導が認められた。以上の結果はHGFは成熟ラット脳内において脳傷害後の神経細胞の生存繊維効果を通じて脳組織の維持に働き得る新たなneurotrophic factorであることを強く示唆するものである。

Research Products
(20 results)

All Other

All Publications (20 results)

[Publications] H.Okazaki: "Prtial purification and characterizaiton of “Injurin-like factor"which stimulates production of hepatocyte growth factor." Biochem.Biophys.Acta. 1220. 291-298 (1994)
[Publications] K.Kawaida: "Hepatocyte growth factor prevent acute renal failure and accelerate renal regeneration." Proc.Nalt.Acad.Sci.USA. 91. 4357-4361 (1994)
[Publications] O.Amano: "Expression and localization of hepatocyte growth factor in rat submandibular gland." Growth Factors. 10. 145-151 (1994)
[Publications] O.F.P.Santos: "Involvement of Hepatocyte growth factor in kidney development." Develop.Biol.163. 525-529 (1994)
[Publications] Y.Itakura: "Autocrine stimulation of motility in SBC-5 human lung carcinoma cells by a two-kringle variant of HGF." Cancer Lett.71. 35-41 (1994)
[Publications] K.Matsumoto: "Hepatocyte growth factor/scatter factor induces tyrosine phosphonlation of focal adhesion kinase(p125FAK)and promotes migration and invasion by oral squamous cell carcinoma cells." J.Biol.Chem.269. 31807-31813 (1994)
[Publications] T.Kobayashi: "Hepatocyte growth factor elevates the activity levels of glycolopid sulfotransferase in renal cell carcionoma cells." Eur.J.Biochrem.219. 407-413 (1994)
[Publications] T.Kobayashi: "Hepatocyte growth factor specifically binds to sulfoglycolipids." J.Biol.Chem.269. 9817-9821 (1994)
[Publications] S.Saito: "Hepatocyte growth factor promotes the growth of cytotrophoblasts by the paracrine system." J.Biochem. 117. 671-676 (1995)
[Publications] N.Nakayama: "Differing distribution of hepatocyte growth factor-positive cells in the liver of LEC rats with acute hepatitis, chronic hepatit:s and hepatoma." Jap.J.Cancer Res.86. 5-9 (1995)
[Publications] K.Matsumoto: "Novel function of prostaglandins as inducer of gene expression of hepatocyte growth factor and putative mediator of tissue regeneration." J.Biochem.117. 458-464 (1995)
[Publications] A.Yamada: "Rapid and sensitive enzyme-linked immunosorbent assay for measurement of HGF in rat and human tissues." Biomed.Res.(in press). (1995)
[Publications] T.Sato: "Hepatocyte growth factor(HGF) is involved in the fomation of osteoclast-like cells mediated by clonal stromal cells(MC3T3-G1/PA6)." J.Cell.Physiol.(in press). (1995)
[Publications] T.Takabayashi: "Hepatocyte growth factor/scatter factor has mitogenic,motogenic and morphogenetic activities on chondrocytes." J.Cell Biol.(in press). (1995)
[Publications] K.Matsumoto: "Pleiotropic roles of HGF in mitogenesis,morphogenesis and organ regeneration." Gann Monograph No.42:Growth Factors;Cell Growth,Morphogenesis and Transformation, 21 (1994)
[Publications] K.Matsumoto: "Hepatotrophic and renotrophic activities of HGF in vivo:Possible application of HGF for hepatic and renal diseases." Springre Verlag, 14 (1994)
[Publications] K.Matsumoto: "Structure,pleiotropic actions,and organotrophic roles of hepatocyte growth factor." Springer Verlag, 21 (1994)
[Publications] K.Matsumoto: "Pleiotropic roles of HGF as a mediator of epithelial-mesenchymal interactions." Organizing Committee for the Eighth International Conference of the International Society of Differentiation., 4 (1994)
[Publications] K.Matsumoto: "Primary and continuous cell culture: Collagenase and Hyaluronidase." John Wiley & Sons Limited.(in press), (1995)
[Publications] K.Matsumoto: "Hepatocyte growth factor as a renotropic factor and therapeutic potential for acute renal failure." Churchill Livingstone(in press), (1995)

1994 Fiscal Year Annual Research Report

HGFによる脳神経系の生存維持とHGFからみた神経変性疾患の病態解析

Principal Investigator

松本 邦夫 大阪大学, 医学部, 講師 (90201780)

Research Products

[Publications] H.Okazaki: "Prtial purification and characterizaiton of “Injurin-like factor"which stimulates production of hepatocyte growth factor." Biochem.Biophys.Acta. 1220. 291-298 (1994)

[Publications] K.Kawaida: "Hepatocyte growth factor prevent acute renal failure and accelerate renal regeneration." Proc.Nalt.Acad.Sci.USA. 91. 4357-4361 (1994)

[Publications] O.Amano: "Expression and localization of hepatocyte growth factor in rat submandibular gland." Growth Factors. 10. 145-151 (1994)

[Publications] O.F.P.Santos: "Involvement of Hepatocyte growth factor in kidney development." Develop.Biol.163. 525-529 (1994)

[Publications] Y.Itakura: "Autocrine stimulation of motility in SBC-5 human lung carcinoma cells by a two-kringle variant of HGF." Cancer Lett.71. 35-41 (1994)

[Publications] K.Matsumoto: "Hepatocyte growth factor/scatter factor induces tyrosine phosphonlation of focal adhesion kinase(p125FAK)and promotes migration and invasion by oral squamous cell carcinoma cells." J.Biol.Chem.269. 31807-31813 (1994)

[Publications] T.Kobayashi: "Hepatocyte growth factor elevates the activity levels of glycolopid sulfotransferase in renal cell carcionoma cells." Eur.J.Biochrem.219. 407-413 (1994)

[Publications] T.Kobayashi: "Hepatocyte growth factor specifically binds to sulfoglycolipids." J.Biol.Chem.269. 9817-9821 (1994)

[Publications] S.Saito: "Hepatocyte growth factor promotes the growth of cytotrophoblasts by the paracrine system." J.Biochem. 117. 671-676 (1995)

[Publications] N.Nakayama: "Differing distribution of hepatocyte growth factor-positive cells in the liver of LEC rats with acute hepatitis, chronic hepatit:s and hepatoma." Jap.J.Cancer Res.86. 5-9 (1995)

[Publications] K.Matsumoto: "Novel function of prostaglandins as inducer of gene expression of hepatocyte growth factor and putative mediator of tissue regeneration." J.Biochem.117. 458-464 (1995)

[Publications] A.Yamada: "Rapid and sensitive enzyme-linked immunosorbent assay for measurement of HGF in rat and human tissues." Biomed.Res.(in press). (1995)

[Publications] T.Sato: "Hepatocyte growth factor(HGF) is involved in the fomation of osteoclast-like cells mediated by clonal stromal cells(MC3T3-G1/PA6)." J.Cell.Physiol.(in press). (1995)

[Publications] T.Takabayashi: "Hepatocyte growth factor/scatter factor has mitogenic,motogenic and morphogenetic activities on chondrocytes." J.Cell Biol.(in press). (1995)

[Publications] K.Matsumoto: "Pleiotropic roles of HGF in mitogenesis,morphogenesis and organ regeneration." Gann Monograph No.42:Growth Factors;Cell Growth,Morphogenesis and Transformation, 21 (1994)

[Publications] K.Matsumoto: "Hepatotrophic and renotrophic activities of HGF in vivo:Possible application of HGF for hepatic and renal diseases." Springre Verlag, 14 (1994)

[Publications] K.Matsumoto: "Structure,pleiotropic actions,and organotrophic roles of hepatocyte growth factor." Springer Verlag, 21 (1994)

[Publications] K.Matsumoto: "Pleiotropic roles of HGF as a mediator of epithelial-mesenchymal interactions." Organizing Committee for the Eighth International Conference of the International Society of Differentiation., 4 (1994)

[Publications] K.Matsumoto: "Primary and continuous cell culture: Collagenase and Hyaluronidase." John Wiley & Sons Limited.(in press), (1995)

[Publications] K.Matsumoto: "Hepatocyte growth factor as a renotropic factor and therapeutic potential for acute renal failure." Churchill Livingstone(in press), (1995)

松本邦夫大阪大学, 医学部, 講師 (90201780)