1994 年度実績報告書

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

研究課題

研究課題/領域番号	06272221
研究機関	大阪大学
研究代表者	松本邦夫大阪大学, 医学部, 講師 (90201780)
キーワード	HGF / c-met / 神経栄養因子 / 脳傷害
研究概要	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。

研究成果
(20件)

すべてその他

すべて文献書誌 (20件)

[文献書誌] H.Okazaki: "Prtial purification and characterizaiton of “Injurin-like factor"which stimulates production of hepatocyte growth factor." Biochem.Biophys.Acta. 1220. 291-298 (1994)
[文献書誌] K.Kawaida: "Hepatocyte growth factor prevent acute renal failure and accelerate renal regeneration." Proc.Nalt.Acad.Sci.USA. 91. 4357-4361 (1994)
[文献書誌] O.Amano: "Expression and localization of hepatocyte growth factor in rat submandibular gland." Growth Factors. 10. 145-151 (1994)
[文献書誌] O.F.P.Santos: "Involvement of Hepatocyte growth factor in kidney development." Develop.Biol.163. 525-529 (1994)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] T.Kobayashi: "Hepatocyte growth factor elevates the activity levels of glycolopid sulfotransferase in renal cell carcionoma cells." Eur.J.Biochrem.219. 407-413 (1994)
[文献書誌] T.Kobayashi: "Hepatocyte growth factor specifically binds to sulfoglycolipids." J.Biol.Chem.269. 9817-9821 (1994)
[文献書誌] S.Saito: "Hepatocyte growth factor promotes the growth of cytotrophoblasts by the paracrine system." J.Biochem. 117. 671-676 (1995)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] A.Yamada: "Rapid and sensitive enzyme-linked immunosorbent assay for measurement of HGF in rat and human tissues." Biomed.Res.(in press). (1995)
[文献書誌] 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)
[文献書誌] T.Takabayashi: "Hepatocyte growth factor/scatter factor has mitogenic,motogenic and morphogenetic activities on chondrocytes." J.Cell Biol.(in press). (1995)
[文献書誌] 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)
[文献書誌] K.Matsumoto: "Hepatotrophic and renotrophic activities of HGF in vivo:Possible application of HGF for hepatic and renal diseases." Springre Verlag, 14 (1994)
[文献書誌] K.Matsumoto: "Structure,pleiotropic actions,and organotrophic roles of hepatocyte growth factor." Springer Verlag, 21 (1994)
[文献書誌] 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)
[文献書誌] K.Matsumoto: "Primary and continuous cell culture: Collagenase and Hyaluronidase." John Wiley & Sons Limited.(in press), (1995)
[文献書誌] K.Matsumoto: "Hepatocyte growth factor as a renotropic factor and therapeutic potential for acute renal failure." Churchill Livingstone(in press), (1995)

1994 年度 実績報告書

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

研究代表者

松本 邦夫 大阪大学, 医学部, 講師 (90201780)

研究成果

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

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

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

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

[文献書誌] 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)

[文献書誌] 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)

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

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

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

[文献書誌] 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)

[文献書誌] 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)

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

[文献書誌] 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)

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

[文献書誌] 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)

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

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

[文献書誌] 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)

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

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

1994 年度実績報告書

松本邦夫大阪大学, 医学部, 講師 (90201780)