1992 Fiscal Year Annual Research Report

血小板因子による肝再生の開始と停止機構の研究

Research Project

Project/Area Number	01440092
Research Institution	KYUSHU UNIVERSITY
Principal Investigator	中村敏一九州大学, 理学部, 教授 (00049397)
Co-Investigator(Kenkyū-buntansha)	松本邦夫九州大学, 理学部, 助手 (90201780) 原野友之九州大学, 理学部, 助手 (80037275) 水野健作九州大学, 理学部, 助教授 (70128396)
Keywords	HGF / 肝再生因子 / 腎再生因子 / インジュリン
Research Abstract	1.HGF投与によるin vivoでの肝再生促進:HGFが肝再生因子の本体として機能していることをリコンビナントヒトHGFを動物に投与することにより証明した。30%部分肝切除マウスにHGFを1μg及び5μgの用量で尾静脈より投与すると、その24時間後に肝細胞の増殖が用量依存的に促進され、5μg投与では最大の肝再生時に匹敵するラベリングインデックス(約30%)が得られた。同様な結果はイヌやラットを用いた実験でも確認された。またHGFは肝細胞の増殖を促進するだけでなく、肝臓毒のANIT投与により誘起された肝炎に対しても用量依存的に強い抗肝炎肝細胞保護作用を有することを明らかにした。 2.腎再生因子としてのHGF:片側腎摘出及びHgCl_2などの腎臓毒による腎傷害時においてもHGFの速やかな発現誘導と、HGFレセプターのダウンレギュレーションが認められ、HGFが腎再生因子として機能していることが示唆された。このことは腎傷害マウスHGFを投与すると、腎再生が強く促進されること、さらに、HGFはHgCl_2投与による急性腎不全を強く防止し、腎機能の保護効果が認められることなどからin vivoで証明された。 3.HGFの発現調節因子:器官の傷害に伴って血中に分泌されるHGF誘導因子を見出し、部分精製後、未知タンパク質性のサイトカインであることを明らかにしインジュリンと命名した。インジュリン以外にもIL-1やTNF-αがHGF発現誘導活性を有すること、また、逆にTGF-β1やグルココルチコイドはHGF発現を強く抑制するサプレッサーであることを明らかにした。またヘパリンはIL-1やTNF-αと異なりHGFmRNA発現を誘導しないが、HGF合成を促進し、HGF産生を誘導する。HGFの発現は正負の因子により調節を受けており、傷害後の器官再生や創傷治癒過程に重要な役割を担っていると考えられる。

Research Products
(19 results)

All Other

All Publications (19 results)

[Publications] G.Shiota,D.B.Rhoads,T.C.Wang,T.Nakamura and E.V.Schmidt: "Hepatocyte growth inhibits growth of hepatocellular carcinoma cells." Proc.Natl.Acad.Sci.USA. 89,. 373-377 (1992)
[Publications] H.Tajima,O.Higuchi,K.Mizuno and T.Nakamura: "Tissue distribution of hepatocyte growht receptor and its exclusive down-regulation in a regenerating organ after injury." J.Biochem.111,. 401-406 (1992)
[Publications] K.Yanagita,M.Nagaike,H.Ishibashi,Y.Niho,K.Matsumoto and T.Nakamura: "Lung may have an endocrine function producing hepatocyte growth factor in response to injury of distal organs." Biochem.Biophys.Res.Commun.182,. 802-809 (1992)
[Publications] S.Osada,S.Nakashima,S.Saji,T.Nakamura,and Y.Nozawa: "Hepatocyte growth factor(HGF)mediates the sustained formation of1,2-diacylglycerol via phosphatidylcholine-phospholipase C in cultured rat hepatocytes." FEBS.Lett.297,. 271-274 (1992)
[Publications] K.Matsumoto,H.Tajima,M.Hamanoue,S.Kono,T.Kinoshita and T.Nakamura: "Identification and characterization of¨injurin¨,an inducer of expression of the gene for hepatocyte growth factor." Proc.Natl.Acad.Sci.USA,. 89,. 3800-3804 (1992)
[Publications] G.Ramadori,K.Neubauer,M.Odenthal,T.Nakamura,T.Knittel,S.Chwogler,and K.H.Meyer zum Buschenfelde: "Hepatocyte Growth Factor(Hepatopoietin a,Scatter Factor)-Gene is expressed in ¨Quiescent¨Fat-Storing(Ito)cells of rat liver:downregulation by transforming growth factor-b" Biochem.Biophys.Res.Commun.183,. 739-742 (1992)
[Publications] H.Tajima,K.Matsumoto and T.Nakamura: "Regulation of cell growth and motility by hepatocyte growth factor and receptor expression in various cell species." Exp.Cell Res.202,. 423-431 (1992)
[Publications] M.Hamanoue,K.Kawaida,S.Takao,H.Shimazu,S.Noji,K.Matsumoto and T.Nakamura: "Expression of the c-met proto-oncogene in COS cells is required for hepatocyte growth factor high affinity binding and mitogenic signal transduction." FEBS Lett.301,. 282-286 (1992)
[Publications] O.Higuchi,K.Mizuno,G.F.Vande Woude and T.Nakamura: "Rapid and marked induction of HGF mRNA in liver and HGF activity in serum of rats after ischemic of crush liver injury." Hepatology. 16,. 1485-1492 (1992)
[Publications] S.Kono,M.Nagaike,K.Matsumoto,and T.Nakamura: "Marked induction of hepatocyte growth growth factor mRNA in intact kidney and spleen in response to injury of distan organ." Biochem.Biophys.Res.Commun.186,. 991-998 (1992)
[Publications] A.J.Marker,E.Galloway,S.Palmer,T.Nakamura,G.W.Gould,R.N.M.MacSween,and M.Bushfield: "Role of the adenylate cyclase,phosphoinositidase c and receptor tyrosine kinase system in the control of hepatocyte proliferation by hepatocyte growth factor." Biochemical.Pharmacol.44,. 1037-1043 (1992)
[Publications] Y.Ishiki,H.Ohnishi,Y.Muto,K.Matsumoto and T.Nakamura: "Direct evidence that hepatocyte growth factor is a hepatotrophic factor for liver regeneration and for potent anti-hepatitis action in vivo." Hepatology. 16,. 1227-1235 (1992)
[Publications] M.S.Pepper,K.Matsumoto,T.Nakamura,L.Orci and R.Montesano: "Hepatocyte growth factor induces urokinase-type plasminogen activator and plasminogen activator inhibitor-1in MDCK epithelal cells." J.Biol.Chem.267,. 20493-20496 (1992)
[Publications] M.Masuhara,S.L.Katyal,T.Nakamura and H.Shi-nozuka: "Differential expression of hepatocyte growth factor,transforming growth factor-alpha and transforming growth factor-betal mRNAs in two experinental models of liver cell proliferation." Hepatology,. 16,. 1241-1249 (1992)
[Publications] K.Matsumoto,H.Tajima,H.Okazaki,and T.Nakamura: "Negative regulation of hepatocyte growth factor gene expression in human lung fibroblasts and leukemic cells by transforming growth factor-β1and glucocorticoids" J.Biol.Chem.267,. 24917-24920 (1992)
[Publications] M.Kagoshima,T.Kinoshita,T.Matsumoto and T.Nakamura: "Changes in expression of mRNA and receptor for hepatocyte growth factor in liver,kidney and lung during postnatal development in rats." Eur.J.Biochem.210,. 375-380 (1992)
[Publications] S.Rong,M.Bdescot,D.Blair,J.Dunn,T.Nakamura,K.Mizuno,M.Park,A.Chan,S.Aaronson,and G.F.Vande Woude: "Tumorigenicity of the met protooncogene and the gene for hepatocyte growth factor." Mol.Cell Biol.12,. 5152-5158 (1992)
[Publications] K.Mizuno and T.Nakamura: "Hepatocyte Growth Factor-Scatter Factor and C-Met Receptor(分担)" Birkhauser Verlag, PP.1-29 (1993)
[Publications] K.Matsumoto and T.Nakamura: "Hepatocyte Growth Factor-Scatter Factor and C-Met Receptor(分担)" Birkhauser Verlag, PP.225-249 (1993)

1992 Fiscal Year Annual Research Report

血小板因子による肝再生の開始と停止機構の研究

Principal Investigator

中村 敏一 九州大学, 理学部, 教授 (00049397)

Research Products

[Publications] G.Shiota,D.B.Rhoads,T.C.Wang,T.Nakamura and E.V.Schmidt: "Hepatocyte growth inhibits growth of hepatocellular carcinoma cells." Proc.Natl.Acad.Sci.USA. 89,. 373-377 (1992)

[Publications] H.Tajima,O.Higuchi,K.Mizuno and T.Nakamura: "Tissue distribution of hepatocyte growht receptor and its exclusive down-regulation in a regenerating organ after injury." J.Biochem.111,. 401-406 (1992)

[Publications] K.Yanagita,M.Nagaike,H.Ishibashi,Y.Niho,K.Matsumoto and T.Nakamura: "Lung may have an endocrine function producing hepatocyte growth factor in response to injury of distal organs." Biochem.Biophys.Res.Commun.182,. 802-809 (1992)

[Publications] S.Osada,S.Nakashima,S.Saji,T.Nakamura,and Y.Nozawa: "Hepatocyte growth factor(HGF)mediates the sustained formation of1,2-diacylglycerol via phosphatidylcholine-phospholipase C in cultured rat hepatocytes." FEBS.Lett.297,. 271-274 (1992)

[Publications] K.Matsumoto,H.Tajima,M.Hamanoue,S.Kono,T.Kinoshita and T.Nakamura: "Identification and characterization of¨injurin¨,an inducer of expression of the gene for hepatocyte growth factor." Proc.Natl.Acad.Sci.USA,. 89,. 3800-3804 (1992)

[Publications] H.Tajima,K.Matsumoto and T.Nakamura: "Regulation of cell growth and motility by hepatocyte growth factor and receptor expression in various cell species." Exp.Cell Res.202,. 423-431 (1992)

[Publications] M.Hamanoue,K.Kawaida,S.Takao,H.Shimazu,S.Noji,K.Matsumoto and T.Nakamura: "Expression of the c-met proto-oncogene in COS cells is required for hepatocyte growth factor high affinity binding and mitogenic signal transduction." FEBS Lett.301,. 282-286 (1992)

[Publications] O.Higuchi,K.Mizuno,G.F.Vande Woude and T.Nakamura: "Rapid and marked induction of HGF mRNA in liver and HGF activity in serum of rats after ischemic of crush liver injury." Hepatology. 16,. 1485-1492 (1992)

[Publications] S.Kono,M.Nagaike,K.Matsumoto,and T.Nakamura: "Marked induction of hepatocyte growth growth factor mRNA in intact kidney and spleen in response to injury of distan organ." Biochem.Biophys.Res.Commun.186,. 991-998 (1992)

[Publications] Y.Ishiki,H.Ohnishi,Y.Muto,K.Matsumoto and T.Nakamura: "Direct evidence that hepatocyte growth factor is a hepatotrophic factor for liver regeneration and for potent anti-hepatitis action in vivo." Hepatology. 16,. 1227-1235 (1992)

[Publications] M.S.Pepper,K.Matsumoto,T.Nakamura,L.Orci and R.Montesano: "Hepatocyte growth factor induces urokinase-type plasminogen activator and plasminogen activator inhibitor-1in MDCK epithelal cells." J.Biol.Chem.267,. 20493-20496 (1992)

[Publications] M.Masuhara,S.L.Katyal,T.Nakamura and H.Shi-nozuka: "Differential expression of hepatocyte growth factor,transforming growth factor-alpha and transforming growth factor-betal mRNAs in two experinental models of liver cell proliferation." Hepatology,. 16,. 1241-1249 (1992)

[Publications] K.Matsumoto,H.Tajima,H.Okazaki,and T.Nakamura: "Negative regulation of hepatocyte growth factor gene expression in human lung fibroblasts and leukemic cells by transforming growth factor-β1and glucocorticoids" J.Biol.Chem.267,. 24917-24920 (1992)

[Publications] M.Kagoshima,T.Kinoshita,T.Matsumoto and T.Nakamura: "Changes in expression of mRNA and receptor for hepatocyte growth factor in liver,kidney and lung during postnatal development in rats." Eur.J.Biochem.210,. 375-380 (1992)

[Publications] S.Rong,M.Bdescot,D.Blair,J.Dunn,T.Nakamura,K.Mizuno,M.Park,A.Chan,S.Aaronson,and G.F.Vande Woude: "Tumorigenicity of the met protooncogene and the gene for hepatocyte growth factor." Mol.Cell Biol.12,. 5152-5158 (1992)

[Publications] K.Mizuno and T.Nakamura: "Hepatocyte Growth Factor-Scatter Factor and C-Met Receptor(分担)" Birkhauser Verlag, PP.1-29 (1993)

[Publications] K.Matsumoto and T.Nakamura: "Hepatocyte Growth Factor-Scatter Factor and C-Met Receptor(分担)" Birkhauser Verlag, PP.225-249 (1993)

中村敏一九州大学, 理学部, 教授 (00049397)