2000 Fiscal Year Annual Research Report

新規神経栄養因子としてのHGFファミリーの発現・機能解析と神経疾患への適用

Research Project

Project/Area Number	12680752
Research Institution	Osaka University
Principal Investigator	船越洋大阪大学, 医学系研究科, 助手 (40273685)
Co-Investigator(Kenkyū-buntansha)	中村敏一大阪大学, 医学系研究科, 教授 (00049397)
Keywords	Hepatocyte Growth Factor(HGF) / HGF-like protein(HLP) / c-Met / Ron / 神経栄養因子 / トランスジェニックマウス / 神経変性疾患 / 運動ニューロン
Research Abstract	(1)大脳皮質形成におけるHGFおよびc-Metの発現解析大脳皮質層構造形成過程で最も重要なE14からE18までの間に、HGFとc-Metの発現がダイナミックに変動していくことを、競合的RT-PCR法および多重免疫染色で明かとした。特に神経突起に対するc-Metの免疫染色性は一過性であることから、HGFのneuritegenesisに対する一過性の機能が示唆された。 (2)大脳皮質ニューロンに対する種々のin vitro神経栄養作用 (1)HGFは初代培養大脳皮質ニューロンの血清除去による神経細胞死をを濃度依存性に阻止した。 (2)HGFは初代培養大脳皮質ニューロンのmigrationを促進した。 (3)一方HGFは大脳皮質ニューロンおよびその前駆細胞の早い増殖は促進しなかった。 (3)網膜形成過程におけるHGFおよびc-Metの発現解析 HGFとc-Metは網膜形成過程で発現制御をうけ、光受容体における発現は成体における重要な機能を示唆した。 (4)神経変性疾患、中でも筋萎縮性側索硬化症(ALS)モデルマウスに対するHGFの機能の解析 (1)神経特異的HGF発現トランスジェニックマウス(HGF-Tg)を作成した。 (2)ALSモデルトランスジェニックマウス(ALS-Tg)とHGF-Tgのダブルトランスジェニックマウスを作成した。 (3)上記の解析結果、HGF遺伝子をALS-Tgの神経細胞に直接長期間発現させることで、ALSの進行を遅延し延命効果が得られることが明らかとなった。 (5)HGFファミリー分子(HLP)の新規神経栄養因子としての同定と発現解析 (1)HLPは微量の他の神経栄養因子共存下でニワトリ胚の末梢神経節の神経突起伸長と細胞移動を促進した。この作用はHLPの受容体Ronの細胞外ドメインとIgGのFcとの融合蛋白(Ron-Fc)で阻害されたことから、HLPと微量の他の神経栄養因子による神経栄養活性はRon/HLP受容体のシグナルに依存していることが明らかとなった。 (2)マウス末梢神経節におけるHGF,HLP,c-Met,Ronの発生過程における発現解析を行った。

Research Products

(28 results)

All Other

All Publications (28 results)

[Publications] K.Nakamura,H.Funakoshi 他: "Molecular Cloning and Functional Characterization of a Human Scavenger Receptor with C-Type Lectin (SRCL) , a Novel Member of a Scavenger Receptor Family."Biochem Biophys Res Commun.. 280(4). 1028-1035 (2001)
[Publications] T.Sumi et al.: "Specific activation of LIM-kinase 2 via threonine-505 phosphorylation by ROCK under the control of Rho."J.Biol.Chem.. 276. 670-676 (2001)
[Publications] T.Takahashi: "Functional involvement of LIM-kinase in Xenopus oocyte maturation."Develop.Biol.. 229. 554-567 (2001)
[Publications] W.Sun,H.Funakoshi 他: "A sensitive quantification method for evaluating the level of hepatocyte growth factor and c-met/HGF receptor mRNAs in the nervous system using competitive RT-PCR."Brain Res Protoc.. 5(2). 190-197 (2000)
[Publications] G.Shiota: "In vivo transfer of hepatocyte growth factor gene accelerantes proliferation of hepatic oval cells in a 2-acetylaminofluorene/partial hepatectomy model in rats."FEBS Lett.. 470. 325-330 (2000)
[Publications] 船越洋,松本邦夫,中村敏一: "HGFの神経系における機能と神経疾患治療への展望"神経研究の進歩. 44(3). 414-422 (2000)
[Publications] S.Radaeva: "Unique epithelial cell production of hepatocyte growth factor/scatter factor by putative precancerous intestinal metaplasias and associated "intestinal-type" of biliary cancer chemically-induced in rat liver."Hepatology. 31. 1257-1265 (2000)
[Publications] J.-M.Otte: "Functional expression of HGF and its receptor in human colorectol Cancer."Digestion. 61. 237-246 (2000)
[Publications] O.Muto: "HGF/SF-induced spreading of MDCK cells corelates with disappearance of barmotin/7H6, a tight junction-associated protein, from the cell membrane."Cell Biol.Intern.. 24. 439-446 (2000)
[Publications] T.Kikuchi: "Secretory leukoprotease inhibitor angments hepatocyte growth factor production in human lung fibroblasts."Am.J.Respir.Cell Mol.Biol.. 23. 364-370 (2000)
[Publications] K.Hayashi: "In vivo transfer of human hepatocyte growth factor gene accelerates re-endothelization and inhibition neointimal formation after balloon injury in rat model."Gene Therapy. 7. 1664-1671 (2000)
[Publications] H.Nakagami: "Anti-apoptotic action of hepatocyte growth factor through mitogen-activated protein kinase on human aortic endothelial cells."J.Hypertension. 18. 1411-1420 (2000)
[Publications] T.Nakamura: "Myocardial protection from infarction by endogenous and exogenous hepatocyte growth factor."J.Clin.Invest.. 106. 1511-1519 (2000)
[Publications] K.Kuba: "HGF/NK4, a four-kingle fragment of hepatocyte growth factor, is an angiogenesis inhibitor that suppresses tumor growth and metastasis in mice."Cancer Res.. 60. 6737-6743 (2000)
[Publications] S.Hiscox: "Inhibition of HGF/SF-induced breast cancer cell matility and invasion by the HGF/SF variant, NK4."Breast Cancer Res. & Treat.. 59. 245-254 (2000)
[Publications] M.Nakano: "Hepatocyte growth factor is essential for amelioration of hyperglycemia in strepto zotocin-induced diabetic mice receiving a marginal mass of intrahepatic islet grafts."Transplantation. 69. 214-221 (2000)
[Publications] S.Mizuno: "Reciprocal balance of hepatocyte growth factor and transforming growth factor-β1 in renal fibrosis in mice"Kidney Intern.. 57. 937-948 (2000)
[Publications] K.Beppu: "Elevation of serum hepatocyte growth factor concentration in patients with gastric cancer is mediated by production by tumor tissue."Anticancer Res.. 20. 1263-1268 (2000)
[Publications] M.Aoki: "Angiogenesis induced by hepatocyte growth factor in non-infarcted myocardium and infarcted myocardium : up-regalation of essential transcription factor for angiogenesis, ets."Gene Therapy. 7. 417-427 (2000)
[Publications] T.Yamada: "Enhanced expression of hepatocyte growth factor by pulmonary ischemia reperfusion injury in the rat."Am.J.Resp.Crit Care Med.. 162. 707-715 (2000)
[Publications] Y.Taniyama: "Potential contribution of a novel anti-fibrotic factor, hepatocyte growth factor, to prevention of myocardial fibrosis by angiotensin II blockade in cardiomyopathic hamster."Circulation. 102. 246-252 (2000)
[Publications] T.Kunisada: "Keratinocyte expression of transgenic hepatocyte growth factor (HGF) affects melanocyte development, leading to dermal melanocytosis."Mech.Dev.. 94. 67-78 (2000)
[Publications] K.Kuba: "Kringle 1-4 of hepatocyte growth factor inhibits proliferation and migration of human microvascular endothelial cells."Biocem.Biophys.Res.Commun.. 279. 846-852 (2000)
[Publications] K.Matsumoto: "Hepatocyte growth factor in renal regeneration, renal disease, and potential therapeutics."Hypertension. 9. 395-402 (2000)
[Publications] G.H.Lai: "Unique epithelial cell production of hepatocyte growth factor/scatter factor by putative precancerous intestinal metaplasias and associated "intestinal-type" biliary cancer chemically induced in rat liver."Hepatology. 31. 1257-1265 (2000)
[Publications] K.Matsumoto: "Hepatocyte growth factor and met in tumor invasion-metastasis : Mechanisms related to cancer prevention.In "Cancer metastasis,molecular and cellular biology and clinical aspects""Academic Publishers. 143-193 (2000)
[Publications] 船越洋他(中村敏一監訳): "増殖因子と受容体/Growth Factors and Receptors : A Practical Approach"メディカル・サイエンス・インターナショナル. 258(1-77) (2000)
[Publications] 船越洋他(中村敏一監訳): "アット・ザ・ベンチ:バイオ研究完全指南"メディカル・サイエンス・インターナショナル. 475(74-103) (2000)

2000 Fiscal Year Annual Research Report

新規神経栄養因子としてのHGFファミリーの発現・機能解析と神経疾患への適用

Principal Investigator

船越 洋 大阪大学, 医学系研究科, 助手 (40273685)

Research Products

[Publications] K.Nakamura,H.Funakoshi 他: "Molecular Cloning and Functional Characterization of a Human Scavenger Receptor with C-Type Lectin (SRCL) , a Novel Member of a Scavenger Receptor Family."Biochem Biophys Res Commun.. 280(4). 1028-1035 (2001)

[Publications] T.Sumi et al.: "Specific activation of LIM-kinase 2 via threonine-505 phosphorylation by ROCK under the control of Rho."J.Biol.Chem.. 276. 670-676 (2001)

[Publications] T.Takahashi: "Functional involvement of LIM-kinase in Xenopus oocyte maturation."Develop.Biol.. 229. 554-567 (2001)

[Publications] W.Sun,H.Funakoshi 他: "A sensitive quantification method for evaluating the level of hepatocyte growth factor and c-met/HGF receptor mRNAs in the nervous system using competitive RT-PCR."Brain Res Protoc.. 5(2). 190-197 (2000)

[Publications] G.Shiota: "In vivo transfer of hepatocyte growth factor gene accelerantes proliferation of hepatic oval cells in a 2-acetylaminofluorene/partial hepatectomy model in rats."FEBS Lett.. 470. 325-330 (2000)

[Publications] 船越洋,松本邦夫,中村敏一: "HGFの神経系における機能と神経疾患治療への展望"神経研究の進歩. 44(3). 414-422 (2000)

[Publications] S.Radaeva: "Unique epithelial cell production of hepatocyte growth factor/scatter factor by putative precancerous intestinal metaplasias and associated "intestinal-type" of biliary cancer chemically-induced in rat liver."Hepatology. 31. 1257-1265 (2000)

[Publications] J.-M.Otte: "Functional expression of HGF and its receptor in human colorectol Cancer."Digestion. 61. 237-246 (2000)

[Publications] O.Muto: "HGF/SF-induced spreading of MDCK cells corelates with disappearance of barmotin/7H6, a tight junction-associated protein, from the cell membrane."Cell Biol.Intern.. 24. 439-446 (2000)

[Publications] T.Kikuchi: "Secretory leukoprotease inhibitor angments hepatocyte growth factor production in human lung fibroblasts."Am.J.Respir.Cell Mol.Biol.. 23. 364-370 (2000)

[Publications] K.Hayashi: "In vivo transfer of human hepatocyte growth factor gene accelerates re-endothelization and inhibition neointimal formation after balloon injury in rat model."Gene Therapy. 7. 1664-1671 (2000)

[Publications] H.Nakagami: "Anti-apoptotic action of hepatocyte growth factor through mitogen-activated protein kinase on human aortic endothelial cells."J.Hypertension. 18. 1411-1420 (2000)

[Publications] T.Nakamura: "Myocardial protection from infarction by endogenous and exogenous hepatocyte growth factor."J.Clin.Invest.. 106. 1511-1519 (2000)

[Publications] K.Kuba: "HGF/NK4, a four-kingle fragment of hepatocyte growth factor, is an angiogenesis inhibitor that suppresses tumor growth and metastasis in mice."Cancer Res.. 60. 6737-6743 (2000)

[Publications] S.Hiscox: "Inhibition of HGF/SF-induced breast cancer cell matility and invasion by the HGF/SF variant, NK4."Breast Cancer Res. & Treat.. 59. 245-254 (2000)

[Publications] M.Nakano: "Hepatocyte growth factor is essential for amelioration of hyperglycemia in strepto zotocin-induced diabetic mice receiving a marginal mass of intrahepatic islet grafts."Transplantation. 69. 214-221 (2000)

[Publications] S.Mizuno: "Reciprocal balance of hepatocyte growth factor and transforming growth factor-β1 in renal fibrosis in mice"Kidney Intern.. 57. 937-948 (2000)

[Publications] K.Beppu: "Elevation of serum hepatocyte growth factor concentration in patients with gastric cancer is mediated by production by tumor tissue."Anticancer Res.. 20. 1263-1268 (2000)

[Publications] M.Aoki: "Angiogenesis induced by hepatocyte growth factor in non-infarcted myocardium and infarcted myocardium : up-regalation of essential transcription factor for angiogenesis, ets."Gene Therapy. 7. 417-427 (2000)

[Publications] T.Yamada: "Enhanced expression of hepatocyte growth factor by pulmonary ischemia reperfusion injury in the rat."Am.J.Resp.Crit Care Med.. 162. 707-715 (2000)

[Publications] Y.Taniyama: "Potential contribution of a novel anti-fibrotic factor, hepatocyte growth factor, to prevention of myocardial fibrosis by angiotensin II blockade in cardiomyopathic hamster."Circulation. 102. 246-252 (2000)

[Publications] T.Kunisada: "Keratinocyte expression of transgenic hepatocyte growth factor (HGF) affects melanocyte development, leading to dermal melanocytosis."Mech.Dev.. 94. 67-78 (2000)

[Publications] K.Kuba: "Kringle 1-4 of hepatocyte growth factor inhibits proliferation and migration of human microvascular endothelial cells."Biocem.Biophys.Res.Commun.. 279. 846-852 (2000)

[Publications] K.Matsumoto: "Hepatocyte growth factor in renal regeneration, renal disease, and potential therapeutics."Hypertension. 9. 395-402 (2000)

[Publications] G.H.Lai: "Unique epithelial cell production of hepatocyte growth factor/scatter factor by putative precancerous intestinal metaplasias and associated "intestinal-type" biliary cancer chemically induced in rat liver."Hepatology. 31. 1257-1265 (2000)

[Publications] K.Matsumoto: "Hepatocyte growth factor and met in tumor invasion-metastasis : Mechanisms related to cancer prevention.In "Cancer metastasis,molecular and cellular biology and clinical aspects""Academic Publishers. 143-193 (2000)

[Publications] 船越洋 他(中村敏一監訳): "増殖因子と受容体/Growth Factors and Receptors : A Practical Approach"メディカル・サイエンス・インターナショナル. 258(1-77) (2000)

[Publications] 船越洋 他(中村敏一監訳): "アット・ザ・ベンチ:バイオ研究完全指南"メディカル・サイエンス・インターナショナル. 475(74-103) (2000)

船越洋大阪大学, 医学系研究科, 助手 (40273685)

[Publications] 船越洋他(中村敏一監訳): "増殖因子と受容体/Growth Factors and Receptors : A Practical Approach"メディカル・サイエンス・インターナショナル. 258(1-77) (2000)

[Publications] 船越洋他(中村敏一監訳): "アット・ザ・ベンチ:バイオ研究完全指南"メディカル・サイエンス・インターナショナル. 475(74-103) (2000)