HGFならびにLIMキナーゼによる高次細胞機能の調節とがん特性の研究

• Project/Area Number: 06283216
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas (A)
• Allocation Type: Single-year Grants
• Research Institution: Osaka University
• Principal Investigator: 中村 敏一 大阪大学, 医学系研究科, 教授 (00049397)
• Co-Investigator(Kenkyū-buntansha): 船越 洋 大阪大学, 医学系研究科, 助手 (40273685) ; 小清水 右一 大阪大学, 医学系研究科, 助手 (50281126) ; 松本 邦夫 大阪大学, 医学系研究科, 助教授 (90201780) ; 宮本 一政 大阪大学, 医学部, 助手 (60273679) ; 根本 康夫 大阪大学, 医学部, 助手 (30250088) ; 原 英二 大阪大学, 医学部, 助手 (80263268)
• Project Period (FY): 1994 – 1999
• Project Status: Completed (Fiscal Year 1999)
• Budget Amount: ¥136,000,000 (Direct Cost: ¥136,000,000); Fiscal Year 1999: ¥25,000,000 (Direct Cost: ¥25,000,000); Fiscal Year 1998: ¥25,000,000 (Direct Cost: ¥25,000,000); Fiscal Year 1997: ¥25,000,000 (Direct Cost: ¥25,000,000); Fiscal Year 1996: ¥15,000,000 (Direct Cost: ¥15,000,000); Fiscal Year 1995: ¥23,000,000 (Direct Cost: ¥23,000,000); Fiscal Year 1994: ¥23,000,000 (Direct Cost: ¥23,000,000)
• Keywords: HGF / 肝硬変 / 慢性腎不全 / 器官再生 / 浸潤・転移阻止 / HGFアンタゴニスト / 血管新生 / LIMキナーゼ / 腫瘍血管新生 / 脂肪肝 / 心筋梗塞 / 遺伝子治療 / 劇症肝炎 / Sky / c-Met / 形態形成 / 浸潤・転移 / Fas / Met / 上皮-間葉相互作用 / HLP / Ron / 肺線維症 / c-met / c-sea / インジュリン

Research Abstract

平成6-11年の6年間に私達はHGFが主に上皮細胞や血管内皮細胞などを標的細胞とし、機能的な細胞社会の構築(組織化)に必須な生物活性であるmitogen,motogen,morphogen活性に加え、anti-apoptosis作用による組織破壊の防止やbFGFに匹敵する強いangiogenesis作用を有することを明らかにした。そして私達はHGFが肝再生のみならず腎再生や肺再生など多くの組織器官の再生修復因子であり、一方、発生過程にあっては、肝、腎、肺などの多くの器官形成に必須の因子であることも明らかにした。また組織・器官の形成や再生因子であるHGFは広範囲な臓器傷害や組織破壊によって起こるさまざまな難治性疾患に対して極めて顕著な治療効果を発揮することを多くの疾患モデル動物を用いて実証した。たとえばHGFは劇症肝炎をはじめ、急性腎不全や急性心筋梗塞の発症防止と共に治癒を促し、さらに慢性疾患の肝線維症/肝硬変、腎硬化症、肺線維症などの線維化疾患に対し顕著な発症防止と治癒・機能改善作用を示す。
他方、HGFは癌と宿主の相互作用を介して多くの癌細胞の悪性化に関与すること、この機構が癌細胞が産生分泌するHGF誘導因子(IL-1,bFGF,TGF-α,PGsなど)とそれに応答して宿主間質により産生されるHGFとの間に形成されるHGFインデューサー/HGFループにあることを明らかにした。すなわち癌の浸潤・転移などの癌悪性化をブロックするにはこのループを断ち切ることにあると考えHGF・アンタゴニスト(NK4)を作製した。NK4はヌードマウスを用いたin vivo実験によって多くのヒト悪性癌(胆のう癌、肺癌、乳癌、膵癌なと)の浸潤・転移を抑制した。またNK4には腫瘍血管新生阻害作用もあり、新しい制癌剤になりうると考えられる。
LIMキナーゼ(LIMK)は私達の研究室によりc-seaのチロシンキナーゼドメインをプローブに8年前にクローニングした分子内にLIMドメインとPDZドメインを有するユニークなプロテインキナーゼである。LIMKはアクチン結合タンパク質のコフィリンをリン酸化し、アクチン細胞骨格を制御することが明らかになった。LIMK/はRacのLIMK2はRho/Cdc42の下流でそれぞれlamliopodiaとstress fiber形成/filopodia形成の制御を行っていることを明らかにした。

Research Products

• [Publications] T. Ueki, et al.: "Hepatocyle growth factor gene therapy of liver cirrhosis in rats"Nature Medicine. 5. 226-230 (1999)
• [Publications] Y. Liu, et al.: "Upregulation of hepatocyte growth factor receptor : an amplification and targeting mechanism for hepatocyte growth factor action in acute renal failure"Kidney Intern. 55. 442-453 (1999)
• [Publications] M. Tahara, K. Matsumoto, T. Nukiwa, and T. Nakamura: "Hepatocyte growth factor leads to recovery from alcohol-induced fatty liver in rats"J. Clin. Invest.. 103. 313-320 (1999)
• [Publications] J. Wojta, et al.: "Hepatocyte growth factor increases expression of vascular endothelial growth factor and plasminogen activator inhibitor-1 in human keratinocytes and the vascular endothelial growth factor receptor f1k-1 in human endothelial cells Evidence for a paracrine loop in wound healing"Lab. Invest. 79. 427-438 (1999)
• [Publications] Z. Jiao, et al.: "Effect of D-galactosamine hydrochloride and partial hepatectomy on spontaneous hepatic injury and hepatocarcinogenesis in Long Evans Cinamon rats"Jpn. J. Cancer Res.. 90. 496-504 (1999)
• [Publications] H. Azuma, et al.: "Effect of hepatocyte growth factor on cluonic rejection in rat renal allografts"Transplat. Proc.. 31. 854-855 (1999)
• [Publications] S. Takada, et al.: "Effect of hepatocyte growth factor on tacrolimus-induced nephrotoxicity in spontaneously hypertensive rats"Transpl. Int.. 12. 27-32 (1999)
• [Publications] H. Ueda, et al.: "Gene transfection of hepatocyte growth factor attenuates reperfusion injury in the heart"Annals. Thoracic Surg.. 67. 1726-1731 (1999)
• [Publications] K. Kosai, K. Matsumoto, and T. Nakamura: "Hepatocyte growth factor prevents endotoxin-induced lethal hepatic failure in mice"Hepatology. 30. 151-159 (1999)
• [Publications] R. Hasina, et al.: "Autocrine and paracrine motility factors and their involvement in invasiveness in a human oral carcinoma cell line"Brit. J. Cancer. 80. 1708-1717 (1999)
• [Publications] K. Kitajima, U. Koshimizu and T. Nakamura: "Expression of a novel type of classic cadherin, PB-cadherin in developing brain and limb buds"Develop. Dyn.. 215. 206-214 (1999)
• [Publications] N. Taniura-Matsumoto, K. Matsumoto and T. Nakamura: "Prostaglandin production in mouse mammary carcinoma cells confers invasive growth potential by inducing hepatocyte growth factor in fibroblasts"Brit. J. Cancer. 81. 194-202 (1999)
• [Publications] M. Kato, Y. Kato, T. Nakamura and Y. Sugiyama: "Efficient extraction by the liver governs the overall elimination of hepatocyte growth factor in rats"J. Pharmacol. Exp. Therap.. 290. 373-379 (1999)
• [Publications] Morishita, et al.: "Therapeutic angiogenesis induced by human recombinant hepatocyte growth factor in rabbit hind limb ischemia model as a cytokine supplement therapy"Hypertention. 33. 1379-1384 (1999)
• [Publications] W. G. Jiang, et al.: "Hepatocyte growth factor/scatter factor decreases the expression of occuludin and transendothelial resistance (TER) and increased paracellular permeability inhuman vascular endothelial cells"J. Cell. Pliysiol.. 181. 319-329 (1999)
• [Publications] C. C. Fehlner-Gardiner, et al.: "Characterization of a functional relationship between hepatocyte growth factor and mouse bone marrow-derived mast cells"Differentiation. 65. 27-42 (1999)
• [Publications] S. Deleu, et al.: "Immediate early gene expression in dog thyrocytes in response to growth proliferation and differentiation stimuli"J. Cell. Physiol.. 181. 342-354 (1999)
• [Publications] S. Deleu, et al.: "IFG-1 or insulin, and the TSH cyclic AMP cascade separately control dog and human thyroid cell growth and DNA synthesis, and complement each other in inducing mitogenesis"Mole. Cell. Endocrin.. 149. 41-51 (1999)
• [Publications] S. Hayashi, et al.: "Potential role of hepatocyte growth factor, a novel angiogenic growth factor in peripheral arterial disease : Downregulation of HGF in response to hypoxia in vascular cells"Circulation. 100. II-301-308 (1999)
• [Publications] T. Nagahori, et al.: "Interferon-gamma upregulates the c-MEt/HGF receptor expression in alvedar epithelial cells"Am. J. Respir. Cell Mol. Biol.. 21. 490-497 (1999)
• [Publications] O. Amano, U. Koshimizu, T. Nakamura and S. Iseki: "Enhancement by hepatocyte growth factor (HGF) of bone and cartilage formation during embryonic mouse mandibular development in vitro"Arch. Oral Biol.. 44. 935-946 (1999)
• [Publications] K. Nishimura, et al.: "Prostate stromal cell-derived hepatocyte growth factor induces invasion of prostate cancer cells DU145 through Tumor-stromal interaction"Prostate. 41. 145-153 (1999)
• [Publications] W. Sun, H. Funakoshi and T. Nakamura: "Differential expression of hepatocyte growth factor and its receptor, c-Met in the rat retina during development"Brain Res.. 851. 46-53 (1999)
• [Publications] A. Uchiyama, et al.: "Hepatocyte growth factor and invasion-stimulatory activity are induced in pleural fluid by surgery in lung cancer patients"Br. J. Cancer. 81. 721-726 (1999)
• [Publications] K. Matsumoto, et al.: "Prevention of renal damage by Angiotensin II blockade, accompanied by increased renal hepatocyte growth factor in experimental hypertensive rats"Hypertension. 34. 279-284 (1999)
• [Publications] Y. Okura, et al.: "Analysis of neurotrophic factor of hepatocyte growth factor (HGF) in the adult hypoglossal nerve axotomy model"Eur. J. Neurosci.. 11. 4139-4144 (1999)
• [Publications] T. Sumi, K. Matsumoto, Y. Takai and T. Nakamura: "Confilin phosphorylation and actin cytoskeletal dynamics regulated by Rho-and Cdc42-activated LIM-kinase 2"J. Cell Biol.. 147. 1519-1532 (1999)
• [Publications] M. K. Jones, et al.: "HGF triggers activation of Cox-2 gene in rat gastric epithelical cells Action mediated through the ERK2 signalling pathway"FASEB J.. 13. 2186-2194 (1999)
• [Publications] K. Kawano, et al.: "Phosphorylation of myosin-binding subunit (MBS) of myosin phosphatase by Rho-kinase in vivo"J. Cell Biol.. 147. 1023-1037 (1999)
• [Publications] F. Tamura, et al.: "FK506 promotes liver regeneration by suppressing natural killer cell activity"J. Gastroenterol. and Hepatol.. (in press). (2000)
• [Publications] A. Uchiyama, et al.: "Significance of locally-secreted hepatocyte growth factor after thoracic cancer surgery as a stimulator for postoperative cancer invasion"Jpn. J. Chin. Oncol.. (in press). (2000)
• [Publications] W. G. Jiang, et al.: "Antagonistic effect of NK4, a novel HGF variant, on in vitro angiogenesis of human vascular endothelial cells"Clin. Cancer Res.. (in press). (2000)
• [Publications] S. Hiscox, et al.: "Inhibition of HGF/SF-induced breast cancer cell matility and invasion by the HGF/SF variant, NK4"Breast Cancer Res. & Treat.. (in press). (2000)
• [Publications] M. Nakano, et al.: "Hepatocyte growth factor is essential for amelioration of hyperglycemia in strepto zotocin-induced diabetic mice receiving a marginal mass of intrahepatic islet grafts"Transplantation. (in press). (2000)
• [Publications] T. Yamada, et al.: "Enhanced expression of hepatocyte growth factor by pulmonary ischemia reperfusion injury in the rat"Am. J. Resp. Crit Care Med.. (in press). (2000)
• [Publications] S. Mizuno, et al.: "Reciprocal balance between HGF and TFG-β a key determinant for pathological phenotypes in chronic renal disease"Kidney Intern.. (in press). (2000)
• [Publications] C. Parr, et al.: "NK4, a new HGF/SF variant, is an antagonist to the influence of HGF/SF on the matility and invasion of colon cancer cells"Intern. J. Cancer. (in press). (2000)
• [Publications] 中村敏一: "新しい腫瘍血管新生制御物質-malignostatin(NK4)"細胞工学. 18. 223-225 (1999)
• [Publications] 久場敬司、松本邦夫、中村敏一: "HGFによる血管新生とその分子内クリングル断片(NK4)による腫瘍血管新生阻害"実験医学. 17. 734-740 (1999)
• [Publications] 水野信哉、中村敏一: "HGFによる急性および慢性腎不全の治療"腎と透析. 46. 494-498 (1999)
• [Publications] 久場敬司、中村敏一: "HGFと癌の浸潤・転移"Surgery Frontier 6 (No2) : 27-38. 6. 27-38 (1999)
• [Publications] 小清水右一、中村敏一: "HGF-肝細胞癌に対するHGFの抗腫瘍作用"血液・免疫・腫瘍. 4. 40-45 (1999)
• [Publications] 中村隆弘、中村敏一: "肝再生の分子機序"別冊:医学のあゆみ、消化器疾患. 2. 68-73 (1999)
• [Publications] 久場敬司、中村敏一: "医学研究その15:血管新生(Angiogenesis)"The Lung. 7. 94-99 (1999)
• [Publications] 水野信哉、中村敏一: "肝細胞増殖因子による腎再生"最新医学. 54. 59-69 (1999)
• [Publications] 角智行、中村敏一: "細胞遊走における増殖因子の役割"医学のあゆみ. 191. 137-142 (1999)
• [Publications] 水野信哉、中村敏一: "肝再生とHGF"現代医療. 31. 69-78 (1999)
• [Publications] 松本邦夫、中村敏一: "HGFの臨床応用に向けて"Medical Academy News. 720/721. 12-12 (1999)
• [Publications] 船越洋、中村敏一: "肝細胞増殖因子(HGF)の検査値と各種疾患"日本臨牀. 37. 821-826 (1999)
• [Publications] 小清水右一、中村敏一: "形質転換成長因子(TGF)"日本臨牀. 37. 802-804 (1999)
• [Publications] 中村敏一、大熊勝治: "肝細胞の培養法"細胞生物学実験法. 1. 27-47 (1999)
• [Publications] 中村敏一、小池克郎、関谷剛男、近藤寿人: "タンパク質分析法"分子生物学プロトコール 改訂2版. 11章. 269-284 (1999)
• [Publications] 中村敏一、長澤俊彦: "HGFによる腎疾患の治療"Annual Review 腎臓2000. XII. 233-240 (2000)
• [Publications] M.T.Donato et al.: "Human hepatocyte growth factor down regulated the expression of cytochrome P450 isozymes in human hepatocytes in primaoy culture." J.Pharmacl Exp.Therap.284. 760-767 (1998)
• [Publications] Y.Yo et al.: "Actions of hepatocyte growth factor as a local modulator in the kidney:Potential role in pathogenesis of renal disease." Kindney Intern.53. 50-58 (1998)
• [Publications] D.Schuppan et al.: "Collagens in the liver extracellular matrix hepatocyte growth factor." Gastroenterology.114. 139-152 (1998)
• [Publications] M.Lyon et al.: "Hepatocyte growth factor/scatter factor binds with high affinity to dermatan sulphate." J.Biol.Chem.273. 271-278 (1998)
• [Publications] H.Li et al.: "Hepatocyte gorwht factor stimuolates invasion of gallbladder carcinoma cell lines in vitro." Clin.Exp.Metastasis.16. 74-82 (1998)
• [Publications] S.Nakamura et al.: "A Novel vascular modulator,hepatocyte growth factor(HGF),as a potentlal index of the severity of hypertention." Biochem.Biophys.Res.Commun.242. 238-243 (1998)
• [Publications] K.Liu et al.: "Protamine enhances the proliferative activity of hepatocyte growth factor in rats." Am.J.Physiol.274. G21-G28 (1998)
• [Publications] R.Gal-Levi et al.: "Hepatocyte growth factor plays a dual role in regulating skeletal muscle satellite cell proliferation and differentiation." Biochem.Biophys.Acta.1402. 39-51 (1998)
• [Publications] T.Miyazawa et al.: "Protection of hippocampal neurons from ischemia-induced delayed neuronal death by hepatocyte growth factor:A novel neurotrophic factor." J.Celebral Blood Flow Metabolism.18. 345-348 (1998)
• [Publications] H.Ohmichi et al.: "Hepatocyte growth factor(HGF)acts as a mesenchynal-derived morphogenic factor during fetal lung develpment." Development.125. 1315-1324 (1998)
• [Publications] S.Mizuno et al.: "Hepatocyte growth factor prevents renal fibrosis and dysfunction in a mouse model of chronio renal-disease." J.Clin.Invest.101. 1827-1834 (1998)
• [Publications] S.Yi et al.: "Paracrine effects of hepatocyte growth factor/scatter factor on non-small cell lung carcinoma cell lines." Brit.J.Cancer.77. 2162-2170 (1998)
• [Publications] K.Kosai et al.: "Hepatocyte growth factor abrogates Fas-induced lethal liver apoptosis i mice." Biochem.Biophys.Res.Commun.244. 683-690 (1998)
• [Publications] M.Suzuki et al.: "Stimulation by histamine of TPA-dependent hepatocyte growth factor production in promyelocytic leukemia HL-60 cells." Biosci.Biotechnol.Biochem.62. 1399-1402 (1998)
• [Publications] S.Tanimura et al.: "Activation of the 41-/43 kDa mitogen-activated protein kinase signaling pathway is required for hepatocyte growth factor-induced cell scattering." Oncogene. 17. 57-65 (1998)
• [Publications] T.Motoi et al.: "Coexpression of hepatocyte growth factor and c-met proto-oncogene product in synovialsarcoma." Pathology Intern.48. 769-775 (1998)
• [Publications] K.Matsumoto et al.: "Cooperative interaction between α-chain and β-chain of HGF on c-Met receptor confers ligand-induced receptor lyrosine phosphorylation." J.Biol.Chem.273. 22913-22920 (1998)
• [Publications] K.Date et al.: "Inhibition of tumor growth and invasion by a four-kringle antagonist(HGF/NK4)for hepatocyte growth factor." Oncogene. 17. 3045-3054 (1998)
• [Publications] Y.Yo et al.: "Potential role of hepatocyte growth factor in the maintenance of renal structure:Anti-apoptotic action of HGF on epithelial cells." Kidney Intern.54. 1128-1138 (1998)
• [Publications] K-X.Liu et al.: "Ligand-induced down-regulation of receptor-mediated clearance of hepatocyte growth factor in rats." Am.J.Physiol.274. G21-G28 (1998)
• [Publications] N.Nakano et al.: "Negative regulation of local hepatocyte growth factor(HGF)expression by angiotensin II and transforming growth[actor-β in blood vessels." Hypertension. 32. 444-451 (1998)
• [Publications] H.Takahashi et al.: "A novel transcript encoding truncated LIM-kinase 2 is specifically expressed in male germ cells undergaing meiosis." Biochem.Biophys.Res.Commun.249. 138-145 (1998)
• [Publications] R.Paciucci et al.: "Activation of the UPA/UPA-R system and redistribution of E-cadherin are associated with HGF-induced motility of pancreas tumor cells." Am.J.Pathol.153. 201-212 (1998)
• [Publications] A.Jikkoet al.: "The role of hepatocyte growth factor in growth plate cartilage." J.Bone Miner.Metab.16. 170-177 (1998)
• [Publications] K.Sugahara et al.: "Elevation of serum human hepatocyte growth factor (HGF) level in patients with pneumonectomy during perioperative period." Intensive Care Med.24. 434-437 (1998)
• [Publications] I.Weimar et al.: "Hepatocyte growth factor/scatter factor(HGF/SF)affects proliferation and migration of myeloid leukemic cells." Leukemia. 12. 1195-1203 (1998)
• [Publications] A.Bosch et al.: "Effects of keratinocyte and hepatocyte growth factor in vivo:Implications for retroviral-mediated gene transfer to liver." Human Gene Therapy. 9. 1747-1754 (1998)
• [Publications] S.Nakamura et al.: "Hepatocyte growth factor as a potential index of complication in diabetes mellitus." J.Hypertension. 16. 2019-2026 (1998)
• [Publications] T.Ueki et al.: "Hepatocyte growth factor gene therapy of liver cirrhosis in rats" Nature Medicine. 5. 226-230 (1999)
• [Publications] Y.Liu et al.: "Upregulation of hepatocyte growth factor receptor:an amplification and targeting mechanism for hepatocyte growth factor action in acute renal failure." Kidney Intern.55. 442-453 (1999)
• [Publications] M.Tahara et al.: "Hepatocyte gowth factor leads to recovery from alcohol-induced fatty liver in rats." J.Clin.Invest.103. 313-320 (1999)
• [Publications] K.Matsumoto & T.Nakamura: "Hepatocyte growth factor and Met:Molecular dialogue for tissue organization and repair." Korean J.Biol.Sci.2. 1-8 (1998)
• [Publications] 中村敏一他: "HGFの分子医学-病態生理・診断・治療-" メディカルレビュー社, 221 (1998)
• [Publications] K.Matsumoto & T.Nakamura: "The Proceedings of the Second International Symposium of Tissue Engineering for Therapeutic Use.(in press)" Churchill Livingstone, (1998)
• [Publications] K.Takai, et al.: "Hipatocyte growth factor is constitutively produced by human bone marrow stromal cells and promotes erythropoiesis." Blood. 89. 1560-1565 (1997)
• [Publications] B.Morishita, et al.: "Potential role of endothelium-specific growth factor hepatocyte growth factor,on endothelial damage in diabetes militus." Diabetes. 46. 138-142 (1997)
• [Publications] I.S.Weimar, et al.: "Hepatocyte growth factor/scatter factor(HGF/SF)promotes adhesion of lymphoma cells to extra-cellular matrix molecules via a4b,and a5b,integrens." Blood. 89. 990-1000 (1997)
• [Publications] N.Kawakami, et al.: "Involvement of hepatocyte growth factor in increased integrin expression on Hep G2 cells triggered by adhesion to endothelial cells." Br.J.Cancer. 75. 47-53 (1997)
• [Publications] T.Sakai, et al.: "Hepatocyte growth factor in bronchoalveolar lavage fluid and cells in patients with in flammatory chest diseases of the lower respitatory tract:Defection by RIA and in situ hybridization." Am.J.Respir.Cell Mole Biol.16. 388-397 (1997)
• [Publications] T.Takahashi, et al.: "Xenopus LIM motif-containing protein kinase,XLIMK,is expressed in the developing head structure of the embryo." Develop.Dyn.209. 196-205 (1997)
• [Publications] S.Aoki, et al.: "Activation of Met tyrosine kinase by hepatocyte growth factor is essential for internal ganogenesis in Xenopus embryo." Biochem.Biophys.Res.Commun.234. 8-14 (1997)
• [Publications] Y.Ikeda, et al.: "Bile ductular proliferation in the granulation tissue of rat liver.:Histological and serial reconstruction studies." Biomed.Res.18. 113-127 (1997)
• [Publications] Y.Matsuda, et al.: "Prevential and therapeutic effects in rats of hepatocyte growth factor infusion on liver fibrosis/cirrhosis." Hepatology. 26. 81-89 (1997)
• [Publications] K.Furugori, et al.: "Level of Hepatocyte growth factor and its messenger ribonucleic acid in uncomplecated pregnancies and those complicated by preeclamptia." J.Clin.Endocrinol.& Metabo.82. 2726-2730 (1997)
• [Publications] T.Nakamura, et al.: "Induction of hepatocyte growth factor in fibroblasts by tumor-derived factors affects invasive growth of tumor cells:In vitro analysis of tumor-stromal interaction." Cancer Res.57. 3305-3313 (1997)
• [Publications] T.Imai, et al.: "Sparse distribution of hepatocyte growth factor-producing cells inside hepatocellular foci in rats treated with hepatocarcinogens." Jpn.J.Cancer Res.88. 615-618 (1997)
• [Publications] T.Kaido, et al.: "Continous hepatocyte growth factor supply prevents lipopolysacharide-induced liver injury in rats." FEBS Lett.411. 378-382 (1997)
• [Publications] S.E.Hiscox, et al.: "Expresstion of the HGF/SF receptor c-met,and its ligand in human colon cancers." Cancer Investigations. 15. 513-521 (1997)
• [Publications] R.Morishita, et al.: "Role of hepatocyte growth factor in endothelial regulation:Prevention of high D-glucose induced endothelia lcell death by prostglandins and phosphodiesterase type 3 inhibitor." Diabetologia. 40. 1053-1061 (1997)
• [Publications] H.Li, et al.: "Hepatocyte growth factor stemuolates invasion of gallbladder carcinoma cell lines in vitro." Clin.Exp.Metastasis.15. 484-493 (1997)
• [Publications] K.Liu, et al.: "Existence of two nonliner elimination mechanisms for hepatocyte growth factor in rats." Am.J.Physiol. 273. E891-E897 (1997)
• [Publications] S.Wakitani, et al.: "Hepatocyte growth factor faulitates Cartilage repair:full thickness articular cartilage defect studied in rabbit knee." Acta Orthop.Stand.68. 474-480 (1997)
• [Publications] T.Adachi, et al.: "Possible involvement of pertussis toxin-sensitive G protein in hepatocyte growth factor(HGF)-induced signal transduction in cultured rat hepatocytes." Hepatology.26. 295-300 (1997)
• [Publications] V.R.Wallenius, et al.: "Chromosomal localization of rat hepatocyte growth factor (Hgf)and HGF receptor (Met) and chractrization of HGF receptor cDNA." Mammalian Genome. 8. 661-667 (1997)
• [Publications] N.Nakano, et al.: "Role of antagotensin II in the reguration of a novel vascular modulator,hepatocyte growth factor(HGF),in experimental hypertensive rats." Hypertension. 30. 1448-1454 (1997)
• [Publications] K.Date, et al.: "HGF/NK4 is a specific antagonist for pleiotrophic actions of hepatocyte growth factor." FEBS Lett.420. 1-6 (1997)
• [Publications] A.Schmassman, et al.: "Role of antagotensin II in the reguration of a novel vascular modulator,hepatocyte growth factor(HGF),in experimental hypertensive rats." Gastroenterolgy. 113. 1858-1872 (1997)
• [Publications] U.Koshimizu, et al.: "cDNA cloning,genomic organization and chromosomal localization of the mouse Lim motif-containing kinase,Limk 2 gene." Biochem.Biophys.Res.Commun.241. 243-250 (1997)
• [Publications] M.Yaekashiwa, et al.: "Both simultaneous and delayed administration of hepatocyte growth factor(HGF)repress the fibrotic changes in murine lung injury induced by bleomycin." Am.J.Resp. & Clin.Care Med.156. 1937-1944 (1997)
• [Publications] R.Morishita, et al.: "Potential role of a novel vascular modulator,hepatocyte growth factor(HGF),in cardiovascular disease:characterization and regulation of local HGF system." J.Atherosclerosis and Thrombosis. 4. 12-19 (1997)
• [Publications] U.Koshimizu, et al.: "Hepatotrophic activities of HGF in liver regeneration after injury and the clnical potentiality for liver diseases." “Liver and Environmental Xenobiotics" Narosa-Elsevier Verlag,. 220-229 (1997)
• [Publications] K.Matsumoto, et al.: "HGF :its organotrophic role and therapeutic potential." “Plasminogen-Related Growth Factors". 212. 198-214 (1997)
• [Publications] K.Matsumoto, et al.: "Hepatocyte growth factor(HGF)as a tissue organizer for organogenesis and regeneration." Biochem.Biophys.Res.Commun.(Mini-Review). 239. 639-644 (1997)
• [Publications] K.Matsumoto, et al.: "Pathophysiological aspects and therapeutic potential of hepatocyte growth factor in liver disease." Internal Medicine and Endocrinology:Pathophysiological and clinical interactions(eds by A.Fabbrini and V.Santiemma.). 95-106 (1997)
• [Publications] D.Schuppan, et al.: "Collagens in the liver extracellular matrix hepatocyte growth factor." Gastroenterology.114. 139-152 (1998)
• [Publications] M.Lyon, et al.: "Hepatocyte growth factor/scatter factor binds with high affinity to dermatan sulphate." J.Biol.Chem.273. 271-278 (1998)
• [Publications] Y.Yo, et al.: "Actions of hepatocyte growth factor as a local modulator in the kidney:Potential role in pathogenesis of renal disease." Kindney Intern. 53. 50-58 (1998)
• [Publications] K.Liu et al.: "Protamine enhances the proliferative activity of hepatocyte growth factor in rats." Am.J.Physiol.(in press). (1997)
• [Publications] R.Gal-Levi, et al.: "Hepatocyte growth factor as a potent regulator of skeletal muscle satellite cell proliferation and differentiation." Biochem.Biophys.Acta.(in press). (1997)
• [Publications] K.Liu et al.: "Change in hepatic handling of hepatocyte growth factor duing liver regeneration in rats." Am.J.Physiol.269(in press). (1998)
• [Publications] S.Mizuno, et al.: "Hepatocyte growth factor prevents renal fibrosis and dysfunction in mouse model of chronio renal disease." J.Clin.Invest.(in press). (1998)
• [Publications] H.Ohmichi et al.: "Hepatocyte growth factor(HGF)acts as a mesenchymal-derived morphogenic factor during fetal lung devel pment." Development.(in press). (1998)
• [Publications] T.Miyazawa, et al.: "Protection of hippocampal neurons from ischemia-induced delayed neuronal death by hepatocyte growth factor:A novel neurotrophic factor." J.Celebral Blood Flow Metabolism.(in press). (1998)
• [Publications] M.T.Donato et al.: "Human hepatocyte growth factor down regulated the expression of cytochrome P450 isozymes in human hepatocytes in primaoy culture." J.Pharmacl Exp.Therap.(in press). (1998)
• [Publications] K.Kosai, et al.: "Hepatocyte growth factor abrogates Fas-induced lethal liver apoptosis in mice." Biochem.Biophys.Res.Commun.(in press). (1998)
• [Publications] F.Tamura, et al.: "FK506 promotes liver regeneration by suppressing natural-killer cell activity.natural killer cell activity." J.Gastroenterol.and Hepatol.(in press). (1998)
• [Publications] W.G.Jiang, et al.: "Hepatocyte growth factor/scatter factor,its molecular,cellular and clinical impacts in cancer." Crit.Review Onclo.Hematol.(in press). (1998)
• [Publications] 中村 敏一: "標準分子医化学" 医学書院, 843-852 (1997)
• [Publications] 中村 敏一: "分子生物学プロトコール改訂版 タンパク質の生化学的分析" 南江堂 (印刷中), (1997)
• [Publications] 中村 敏一: "肝臓病-今日の診断と最新の治療" 国際医書出版, 299-310 (1997)
• [Publications] 中村 敏一: "生命体システムの修復" 講談社サイエンティフィック, 124 (1997)
• [Publications] 松本 邦夫, 中村 敏一: "病理学キーワード" 文光社, pp.40 (1997)
• [Publications] N.Nishi: "Changes in gene expression of growth factors and their receptors during castration-induced involusion and androgen-induced regrowth of rat prostate" Prostate. 28. 139-152 (1996)
• [Publications] M.Hamanoue: "Neurotrophic effect of hepatocyte growth factor on CNS neurons in vivo" J.Neurosci.Res.43. 554-564 (1996)
• [Publications] T.Kaido: "Continous HGF supply from spleen ransplanted HGF-expressing fibroblasts prevents CCl_4-induced acute live r injury in rats" Biochem.Biophys.Res.Commun.218. 1-5 (1996)
• [Publications] M.Inui: "Enhanced gene expression of transforming growth factor-α and c-met in rat urinary bladder cancer" Urol.Res.24. 55-60 (1996)
• [Publications] H.Yamazaki: "Biphasic changes in serum hepatocyte growth factor after transcatheter arterial chemoembolization theraphy for hepatocellular carcinoma" Cytokine. 8. 178-182 (1996)
• [Publications] T.Imai: "Expression of hepatocyte growth factor and c-met mRNAs during rat chemically induced hepatocarcinogenesis in the Solt-Farber model" Carcinogenesis. 17. 19-24 (1996)
• [Publications] Y.Kubo: "Hepatocyte proliferation induced in rats by lead nitrate is suppressed by several tumor necrosis factor-α inhibitors" Hepatology. 23. 104-114 (1996)
• [Publications] S.Takada: "Serum HGF levels in acute renal rejection after living related renal transplantation" Transplant.Intern.9. 151-154 (1996)
• [Publications] M.Joaquin: "Hepatocyte growth factor and transforming growth factor beta regulates 6-phosph of ructo-2-kinase/fructose-2,6-bisphos-phatase geneexpression in rat hepatocyte primary cultures" Biochem.J.314. 235-240 (1996)
• [Publications] M.Takahashi: "Constitutive expression of hepatocyte growth factor may maintain the sheet construction of gastric epithelial cells through facilitating actin-myosin contractile system" Biochem.Biophys.Res.Commun.219. 40-46 (1996)
• [Publications] M.J.Tabata: "Hepatocyte growth factor is involved in the morphogenesis of tooth gern in murine molars" Development. 122. 1243-1251 (1996)
• [Publications] Y.Kobayashi: "Induction of hepatocyte growth by intraportal infusion of hepatocyte growth factor into beagle dogs" Biochem.Biophys.Res.Commun.220. 7-12 (1996)
• [Publications] I.Fabregat: "Epidermal growth factor,but not hepatocyte growth factor,suppresses the apoptosis induced by transforming growth factor-beta in fetal hepatocytes in primary culture" FEBS Lett.384. 14-18 (1996)
• [Publications] P.Gines: "Inhibitory actions of cyclic adenosine monophosphate and pertussis toxin define two distinct epidermal growth factor-regulated pathways leading to activation of mitogen-activated protein kinase in rat hepatocytes" Hepatology. 23. 1167-1173 (1996)
• [Publications] K.Sugimoto: "Molecular cloning and characterization of a newly identified member of the cadherin family,PB-cadherin" J.Biol.Chem.271. 11548-11556 (1996)
• [Publications] S.Takada: "HGF prevent tacrolimus(FK506)-induced nephrotoxicity in SHR rats" Transplant.Proc.28. 1089-1090 (1996)
• [Publications] T.Adachi: "Mitogen-activated protein kinase activation in hepatocyte growth factor-stimulated rat hepatocytes:Involvement of protein tyrosine kinase and protein kinase C" Hepatology. 23. 1244-1253 (1996)
• [Publications] M.J.Gomez-Lechon: "Cell cycle progression proteins(cyclins),oncogene expression and signal transduction during the proliferative response of human hepatocytes to hepatocyte growth factor" Hepatology. 23. 1012-1019 (1996)
• [Publications] S.Hayashi: "Autocrine-paraqrine effects of over-expression of hepatocyte growth factor gene on growth of endothelial cells" Biochem.Biophys.Res.Commun.220. 539-545 (1996)
• [Publications] H.Amaike: "Human recombinant HGF prevents lethal side effects of cyclosporin A in mice" Cytokine. 8. 387-394 (1996)
• [Publications] R.J.Mason: "Hepatocyte growth factor is a mitogen for alveolar type ΙΙ cells in rat lavage fluid" Am.J.Physiol.271. L46-L53 (1996)
• [Publications] N.Nakayama: "Hepatocyte growth factor and c-met expression in Long-Evans Cinnamon rats with spontaneous hepatitis and hepatoma" Hepatology. 24. 596-602 (1996)
• [Publications] H.Ohmichi: "In vivo mitogenic action of hepatocyte growth factor on branchial epithelial cells:Pulmotrophic role of HGF in lung regeneration" Am.J.Physiol.270. L1031-L1039 (1996)
• [Publications] M.I.Guillen: "The hepatocyte growth factor regulates the synthesis of acute-phase proteins in human hepatocytes. Divergent effects on IL-6-stimulated genes" Hepatology. 23. 1345-1352 (1996)
• [Publications] K.Matsumoto: "Acquisition of invasive phenotype in gallblader cancer cells via looped interaction of stromal fibroblasts and cancer cells mediated by HGF" Jap.J.Cancer Res.87. 702-710 (1996)
• [Publications] T.Nakamura: "Cloning and expression of xenopus HGF-like protein(HLP)and Ron/HLP receptor implicate their involvement in early neural development" Biochem.Biophys.Res.Commun.224. 564-573 (1996)
• [Publications] H.G.Chang: "Serum Repatocyte growth factor concentration in patients with various degrees of chronic renal failure" Nephrology. 2. 175-179 (1996)
• [Publications] S.Ueno: "Exogenous hepatocyte growth factor markedly stimulates liver regeneration following portal branch ligation in dogs" Cancer Chemoter.and Pharmacol.38. 233-237 (1996)
• [Publications] Y.Nakamura: "A vaschlar modulator,hepatocyte growth factor(HGF),is associated with systolic blood pressure" Hypertension. 28. 409-413 (1996)
• [Publications] E.Ichimura: "Over expression of c-met/HGF receptor in human non small cell lung cancinoma in vitro and in vivo its prognostic significance" Jap.J.Cancer Res.87. 1063-1069 (1996)
• [Publications] K.Matsumoto: "Heparin functions as a hepatotrophic factor by inducing production of hepatocyte growth factor" Biochem.Biophys.Res.Commun.227. 455-461 (1996)
• [Publications] Y.Nakamura: "Hepatocyte growth factor(HGF)is a novel member of endothelium-specific growth factors:additive stimulatory effect of HGF with basic fibroblast growth factor,but not vascular endothelial growth factor" J.Hypertens.14. 1067-1072 (1996)
• [Publications] T.Mizuguchi: "Recovery of mRNA expression of tryptophan 2,3-dioxygenase and serine dehydratase in long-term cultures of primary rat hepatocytes" J.Biochem.120. 511-517 (1996)
• [Publications] A.Uchiyama: "Interleukin 4 inhibits hepatocyte growth factor-induced invasion and migration of colon carcinoma" J.Cell.Biochem.62. 443-453 (1996)
• [Publications] M.Dalmau: "Nitric oxide inhibits DNA synthesis and induces activation of poly(ADP-ribose)polymerase in cultured rat hepatocytes" Exp.Cell Res.228. 14-18 (1996)
• [Publications] Z.G.Han: "Regulaition of motility,invasiveness and growth of lung cancer cells by hepatocyte growth factor/scatter factor" Surg.Res.Commun.18. 217-229 (1996)
• [Publications] W.G.Jiang: "Hepatocyte growth factor induces tyrosine phosphorylation of focal adhesion kinase(FAK)and paxillin and enhances cell matrix interaction" Oncology Reports. 3. 819-823 (1996)
• [Publications] S.Aoki: "Molecular cloning of Xenopus c-met/hepatocyte growth factor receptor and its regional expression during early development" J.Biochem.120. 961-968 (1996)
• [Publications] T.Iwazawa: "Primary human fibroblasts induce diverse tumor invasiveness-Involvement of HGF as an important paracrine factor" Jap.J.Cancer Res.87. 1134-1142 (1996)
• [Publications] S.Kasai: "Hepatocyte growth factor is a paracrine regulator of rat prostate epithelial growth" Biochem.Biophys.Res.Commun.228. 646-652 (1996)
• [Publications] M.Takahashi: "Hepatocyte growth factor as a key to modulate anti-ulcer action of prostaglandins in stomach" J.Clin.Invest.98. 2604-2611 (1996)
• [Publications] G.Shiota: "Inhibitory effect of hepatocyte growth factor on metastosis of hepatocellular carcinoma in transgenic mice" Res.Commun.Mole.Pahol.Pharmacol.91. 33-39 (1996)
• [Publications] T.Adachi: "Phospholipase D activation in hepatocyte growth factor-stimulated rat hepatocytes mediates the expression of c-jun and c-fos:Involvement of protein tyrosine kinase,protein kinase C ,and Ca^<2+>" Hepatology. 24. 1274-1281 (1996)
• [Publications] K.Liu: "Change in hepatic handling of hepatocyte growth factor during liver regeneration in rats" Am.J.Physiol.269(in press). (1996)
• [Publications] N.Torok: "Upregulation of molecular motor encoding genes during HGF-and EGF-induced cell motiliy" J.Biol.Chem.(in press). (1997)
• [Publications] S.Hiscox: "Expression of HGF/SF and its receptor cMET in human colon cancers" Cancer Investigations. (in press). (1997)
• [Publications] G.Shiota: "Coexpression of hepatocyte growth factor and its receptor(c-met oncogene) in HGL 4 glioblastoma cells" Lab.Invest. (in press). (1997)
• [Publications] K.Takai: "Hepatocyte growth factor is constitutively produced by human bone marrow stromal cells and promotes erythropoiesis" Biood. (in press). (1997)
• [Publications] R.Morishita: "Potential role of endothelium-specific growth factor hepatocyte growth factor,on endothelial damage in diabetes militus" Diabetes. (in press). (1997)
• [Publications] I.S.Weimar: "Hepatocyte growth factor/scatter factor (HGF/SF) promotes adhesion of lymphoma cells to extra-cellular matrix molecules via α_4β,and α_5β,integrens" Blood. (in press). (1997)
• [Publications] T.Sakai: "Hepatocyre growth factor in bronchoalveolar lavage fluid and cells in patients with in flammatory chest diseases of the lower respitatory tract:Defection by RIA and in situ hybridization" Am.J.Resp.Cell Mole Biol.(in press). (1996)
• [Publications] Y.Matsuda: "Prevential and therapeutic effects in rats of hepatocyte growth factor on liver fibrosis/cirrhosis" Hepatology. (in press). (1997)
• [Publications] T.Takahashi: "Xenopus LIM motif-containing protein kinase 1 XLIMK 1 is expressed mainly in embryonic neural tissues that develop sensoryorgans" Develop.Dyn.(in press). (1997)
• [Publications] K.Matsumoto: "Emerging multipotent aspects of hepatocyte growth factor" J.Biochem.119. 591-600 (1996)
• [Publications] K.Matsumoto: "HGF in lung morphogenesis and tumor invasion:roles as a mediator in epithelial-mesenchymal and tumor-stromal interactions" Cancer Chemother.and Pharmacol.38. S42-S47 (1996)
• [Publications] 立石紀子、中村敏一: "Hepatocyte Growth Factor,HGF" 動脈硬化. 23. 683-688 (1996)
• [Publications] 天池寿、中村敏一: "HGFによる器官再生とその臨床応用" 治療. 78. 126-128 (1996)
• [Publications] 小清水右一、中村敏一: "解明進む器官形成のメカニズム:生体の組織恒常性を維持する普遍性機能因子としてのHGF" 化学と生物. 35. 8-10 (1996)
• [Publications] U.Koshimizu: "Liver and Environmental Xenobiotics" Narosa-Elsevier Verlag, 10 (1997)
• [Publications] 松本邦夫、青木俊介、中村敏一: "骨形成・吸収シグナリングと骨疾患" 羊土社, 90-96 (1996)
• [Publications] 中村敏一: "バイオサイエンス用語ライブラリー" 羊土社, 232 (1996)
• [Publications] 松本邦夫: "バイオサイエンス用語ライブラリー" 羊土社, 28-31 (1996)
• [Publications] 松本邦夫: "発生・神経 バイオサイエンス用語ライブラリー" 羊土社, 82-83 (1996)
• [Publications] 松本邦夫: "発生・神経 バイオサイエンス用語ライブラリー" 羊土社, 98-99 (1996)
• [Publications] 小清水右一: "発生・神経 バイオサイエンス用語ライブラリー" 羊土社, 44-45 (1996)
• [Publications] 小清水右一: "発生・神経 バイオサイエンス用語ライブラリー" 羊土社, 60-61 (1996)
• [Publications] 小清水右一: "発生・神経 バイオサイエンス用語ライブラリー" 羊土社, 86-88 (1996)
• [Publications] 松本邦夫: "分子細胞生物学辞典" 東京化学同人, 189 (1987)
• [Publications] 小清水右一、中村敏一: "細胞増殖因子研究の最前線‘97-‘98 実験医学増刊" 羊土社(印刷中),
• [Publications] 松本邦夫、中村敏一: "細胞増殖因子研究の最前線‘97-‘98 実験医学増刊" 羊土社(印刷中),
• [Publications] 松本邦夫、中村敏一: "タンパク質の生化学的分析 分子生物学プロトコール改訂第2版" 南江堂(印刷中),
• [Publications] N.Nakayama: "Differing distribution of hepatocyte growth factor-positive cells in the liver of LEC rats with acute hepatitis,chronic hepatitis and hepatoma." Jap.J.Cancer Res.86. 5-9 (1995)
• [Publications] H.Nakamura: "Molecular cloning of Xenopus HGF cDNA,and its expression studied in Xenopus early embryogenesis." Mech.Develop.49. 121-131 (1995)
• [Publications] G.Shiota: "Serum hepatocyte growth factor level:its clinical implication." Hepatology. 21. 106-112 (1995)
• [Publications] W.G.Jiang: "Inhibition of motility and invasion by invasion inhibiting factor-2(11F-2)on human colon cancer cells." Surg.Res.Commun.17. 67-78 (1995)
• [Publications] K.Matsumoto: "Novel funcition of prostaglandins as induccer of gene expression of hepatocyte growth factor." J.Biochem.117. 458-464 (1995)
• [Publications] F.Myokai: "Expression of the hepatocyte growth factor gene during development of the chicken limb." Develop.dynamics. 202. 80-90 (1995)
• [Publications] T.Sato: "Hepatocyte growth factor(HGF)isinvolved in the formation of osteoclast-like cells mediated by clonal stromal cells(MC3T3-G1/PA6)." J.Cell.Physiol.164. 197-204 (1995)
• [Publications] M.J.Gomez-Lechon: "Effect of hepatocyte growth factor(h-rHGF)on the growth and metabolism of human hepatocytes in primary culture." Hepatology. 21. 1248-1254 (1995)
• [Publications] S.Saito: "Hepatocyte growth factor promotes the growth of cytotrophoblasts by the paracrine system." J.Biochem.117. 671-676 (1995)
• [Publications] M.Takahashi: "Hepatocyte growth factor is the most potent endogenous stimulant of rabbit gasric epithelial cell proliferation and migration in primary culture." J.Clin.Invest.95. 1994-2003 (1995)
• [Publications] T.Takabayashi: "Hepatocyte growth factor/scatter factor has mitogenic,motogenic and morphogenetic activities on chondrocytes." J.Cell.Biol.129. 1411-1419 (1995)
• [Publications] K.Matsumoto: "Hepatocyte growth factor as a potent survival factor for rat pheochromocytoma PC12 cells." Exp.Cell Res.220. 71-78 (1995)
• [Publications] S.Seslar: "Tumor-stroma interactions and stromal cell density regulate hepatocyte growth factor protein levels:A role for transforming growth factor-b activation." Endocrinology. 136. 1954-1953 (1995)
• [Publications] A.Yamada: "Rapid and sensitive enzyme-linked immunosorbent assay for measurement of HGF in rat and human tissues." Biomed.Res.16. 105-114 (1995)
• [Publications] E.J.G.Barros: "Differential tubulogenic and branching morphogenetic activities of growth factors:Implications for epithelial tissue development." Proc.Natl.Acad.Sci.USA. 92. 4412-4416 (1995)
• [Publications] H.Shimura: "Induction of invasive growth in a gallbladder cancer cell line by hepatocyte growth factor in vitro." Jap.J.Cancer Res.86. 662-669 (1995)
• [Publications] K.Ohashi: "Molecular cloning,characterization and in situe localization in the brain of rat sky receptor tyrosine kinase." J.Biochem.117. 1267-1275 (1995)
• [Publications] T Adachi: "Roles of prostaglandin production and MAP kinase activation inhepatocyte growth factor-mediated rat hepatocyte proliferation." Hepatology. 21. 1668-1674 (1995)
• [Publications] M.Yaono: "Hepatocyte growth factor enhancement of GST-P postive hepatic foci development in rats treated with diethylnitrosamine and N-ethyl-N-hydroxy ethylnitrosamine." Jap.J.Cancer Res.86. 718-723 (1995)
• [Publications] W.G.Jiang: "Inhibition of HGF/SF-induced membrane ruffling and cell motility by transient elevation of cytosolic free Ca^<2+>." Exp.Cell Res.220. 424-433 (1995)
• [Publications] Y.Mastuda: "Hepatocyte growth factor prevents liver cirrhosis caused by dimethylnitrosamine in rats." J.Biochem.118. 643-649 (1995)
• [Publications] S.Honda: "Localization and functional coupling of HGF and c-Met/HGF receptor in rat brain:implication as neurotrophic factor" Mole.Brain Res.32. 197-210 (1995)
• [Publications] M.R.Vila: "Hepatocyte growth factor is a potent mitogen for normal human pancreas cells in vitro." Lab.Invest.73. 409-418 (1995)
• [Publications] P.Gines: "Tyrosine kinase growth factor receptors but not seven-membrane-spanning or phorbol esters activate mitogen-activated protein kinase in rat hepatocytes." Hepatology. 22. 1296-1303 (1995)
• [Publications] M.Hu: "Human peri-tumoral and lung fibroblasts produce paracrine motility factors for recently established human sarcoma cell strains." Intn.J.Cancer. 62. 585-592 (1995)
• [Publications] Y.Nakamura: "Expression of local hepatocyte growth factor system in vascular tissue." Biochem.Biophys.Res.Commun.215. 483-488 (1995)
• [Publications] M.Takahashi: "Hepatocyte growth factor stimulates wound repair of the rabbit esophageal epithelial cells in primary culture." Biochem.Biophys.Res.Commun.216. 298-305 (1995)
• [Publications] W.G.Jiang: "Induction of tyrosine phosphorylation and translocation of ezrin by hepatocyte growth factor/scatter factor(HGF/SF)." Biochem.Biophys.Res.Commun.217. 1062-1069 (1995)
• [Publications] T.Kaido: "Contininous HGF supply from spleen transplanted HGF-expressing fibroblasts prevents CCI_4-induced acute liver injury in rats." Biochem.Biophys.Res.Commun.218. 1-5 (1996)
• [Publications] K.Matsumoto: "Hepatocyte growth factor as a renotropic factor and therapeutic potential for acute renal failure." Acute Renal Failure:Emerging New Concepts and Therapeutic Strategies., 24 (1995)
• [Publications] H.Amaike: "Takahashi Memorial Forum,Tokyo,5 November 2094,Excepta Medica International" Elsevier ScienceB.V.Amsterdam., 14 (1995)
• [Publications] 中村敏一 監訳: "細胞増殖因子(I.A.McKay and I.M.Leigh編)" マディカル・サイエンス イタ-ナショナル, 232 (1995)
• [Publications] U.Koshimizu: "Liver and Environmental Xenobiotics" Narosa-Elsevier Verlag(in press), (1996)
• [Publications] H.Nakamura: "Molecular clonig of Xenopus HGFcDNA and its expression studies Xenopus early embryogenesis." Mech.Develop.49. 123-131 (1994)
• [Publications] C.deJuan: "Hepatocyle growth factor up-regulates met expression in rat fetal hepatocytes in primary culture." Biochem.Biophys.Res.Commun.204. 1364-1370 (1994)
• [Publications] T.Mitaka: "Effect of mitogens and co-mitogens on the formation of small-cell colonies in primary cultures of rat hepatocytes." J.Cell.Physiol.157. 461-468 (1994)
• [Publications] H.Okazaki: "Prtial purification and characterization of “Injurin-like factor"whichstimulates production of hepatocyte growth factor." Biochem.Biophys.Acta. 1220. 291-298 (1994)
• [Publications] K.Takaishi: "Involvement of rho p21 small GTP-binding protein and its regulatory protein in the HGF-induced cell motility." Oncogene. 9. 273-279 (1994)
• [Publications] K.Ohashi.: "Cloning of novel receptor tyrosine kinase,Sky,predominantly expressedin brain." Oncogene. 9. 699-705 (1994)
• [Publications] K.Mizuno: "Purification and chracterization of hepatocyte growh factor(HGF)-converting enzyme:Activatin of Pro HGF." Biochem.Biophys.Res.Commun.198. 1161-1169 (1994)
• [Publications] K.Mizuno: "Hairpin loop and second kringledomain are essential sites for heparin-binding and biological activity of hepatocyte growth factor." J.Biol.Chem.269. 1131-1136 (1994)
• [Publications] Y.Tanoue: "A specific inhibitor for hepatocyte growth factor(HGF)-Converting enzyme synthesis adn effects on the mitogenic activity of pro-HGF." Peptide Chemistry Protein Research Fundation,Osaka. 201-204 (1994)
• [Publications] S.Bellusci: "Creation of HGF/SF autocrine loop in carcinoma cells induces invasiveproperties associated with increased tumorigenicity." Oncogene. 9. 1091-1099 (1994)
• [Publications] T.Kobayashi: "Hepatocyte growth factor elevates the activity levels of glycolopid sulfotransferase in renal cell carcinoma cell." Eur.J.Biochem.219. 407-413 (1994)
• [Publications] G.Shiota: "Hepatocyte growth factor in transgenic mice:Effects on hepatocyte growth,liver regeneration and gene expression." Hepatology. 19. 962-972 (1994)
• [Publications] G.Shiota: "Hepatocyte growth factor regulates transforming growth factor alpha inHepG2 hepatic cells." Biochem.Biophys.Res.Commun.200. 1099-1104 (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] J.J.Couper: "High glucose and hyprrosmolality stimulate hepatocyte growth factor secrection from cultured human mesangial cells." Diabetologia. 37. 533-535 (1994)
• [Publications] J.W.S.Fang: "Hepatocyte proliferation as an indicator of outcome in acute alcoholic hepatitis." Lancet. 343. 820-823 (1994)
• [Publications] M.Lyon: "The interaction of hepatocyte growth factor with heparan sulphate:Elucidation of the major heparan sulphatestructural determinants." J.Biol.Chem.269. 11216-11223 (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] K.Mizuno: "Identification of a human cDNA encoding anovel protein kinase with two repeats of the LIM/double zinc finger motif in the molecule." Oncogene. 9. 1605-1612 (1994)
• [Publications] S.Dremier: "Mitogenic,dedifferentiating,and scattering effects of hepatocyte growth factor on dog thyroid cells." Endocrinology. 135. 135-140 (1994)
• [Publications] H.Chang: "Blood hepatocyte growth factor levels in chronic renal failure patients." Nephron. 67. 498 (1994)
• [Publications] J.Wojta: "Hepatocyte growth factor stimulates expression of plasminogen activator inhibitor type 1and tissue factor in HepG2 cells in culture." Blood. 84. 151-157 (1994)
• [Publications] Y.Itakura: "Autocrine stimulation of motility in SBC-5 human lung carcinoma cells by a two-kringle variant of HGF." Cancer Lett.83. 235-243 (1994)
• [Publications] K.Ohashi: "Molecular cloning of a chicken lung cDNA encoding a novel protein kinase with N-terminal two LIM/double zinc finger motifs." J.Biochem.116. 636-642 (1994)
• [Publications] H.Shinozuka: "Roles of growth factors and of tumor necrosis factor-α on liver cell proliferation induced in rats by lead nitrate." Lab.Invest.71. 35-41 (1994)
• [Publications] Y.Kato: "Heparin-hepatocyte growth factor(HGF)complex with low plasma clearance and retained hepatocyte proliferating activity." Hepatology. 20. 417-424 (1994)
• [Publications] M.Suzuki: "Cloned cells develop renal cortical collecting tubules." Nephron. 68. 118-124 (1994)
• [Publications] N.Rahimi: "Roles of hepatocyte growth factor in breast cancer:A novel mitogenic factor secreted by adipocytes." DNA and Cell Biol.13. 1189-1197 (1994)
• [Publications] G.Shiota: "Inhibition effect of hepatocytegrowth factor against FaO hepatocellular carcinoma cells may be associated with changes of intracellular signalling pathways mediated by protein kinase." Res.Commun.Chem.Pathol.Pharmacol.85. 271-278 (1994)
• [Publications] M.Takahashi: "Hepatocyte growth factor is the most potent endogenous stimulant of rabbit gastric epithelial cell proliferation and migration in primary culture." J.Clin.Invest.(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: "Hepatocyte growth factor as a potent survival factor for rat pheochromocytoma PC12 cells." Exp.Cell Res.(in press). (1995)
• [Publications] G.Shiota: "Serum hepatocyte growth factor in acute hepatic failure in comparison to acute hepatitis." Res.Commun.Mole.Pathol.Pharmacol.85. 157-162 (1994)
• [Publications] G.Shiota: "Assessment of in vitro growth potential of hepatocyte expressing hepatocyte growth factor in an autocrine fasion." Res.Commun.Mole.Pathol.Pharmacol.85. 151-156 (1994)
• [Publications] M.Joannidis: "Regional expression of hepatocyte growth factor/c-met in experimentalrenal hypertrophy and hyperplasia." Am.J.Physiol.267. F231-F236 (1994)
• [Publications] R.J.Mason: "Hepatocyte growth factor is a growth for rat alveolar typeII cells." Am.J.Respir.Cell Mol.Biol.11. 561-567 (1994)
• [Publications] K.Matsumoto: "Hepatocyte growth factor/scatter factor induces tyrosin phosphonlation of focal adhesion kinsase(p125FAK)and promotes migration and invasion by oral squamous cell carcinoma cells." J.Biol.Chem.269. 31807-31813 (1994)
• [Publications] A.Koj: "Hepatocyte growth factor and retinoic acid exert opposite effects on synthesis of class 1 and class 2 acutephase proteins in rat hepatoma cells." Int.J.Biochem.(in press). (1995)
• [Publications] F.Myokai: "Expression of the hepatocyte growth factor gene during development ofthe chicken limb." Develop.dynamics. (in press). (1995)
• [Publications] T.Sato: "Hepatocyte growth factor(HGF)isinvolved in the formation of osteoclast-like cells mediated by clonal stromal cells(MC3T3-C1/PA6)." J.Cell.physiol.(in press). (1995)
• [Publications] J.V.Soriano: "Hepatocyte growth factor stimulates extensive develoment of branchingduct-like structures by cloned mammary gland epithelial cell." J.Cell Sci.(in press). (1995)
• [Publications] M.J.Gomez-Lechon: "Effect of hepatocyte growth factor(h-rHGF)on the growth and metubolism of human hepatocytes in primary culture." Hepatology. (in press). (1995)
• [Publications] W.G.Jiang: "Anti-motility and anti-invasiveness properties of invasion inhibitingfactor(11F-2)on human colon cancer cells." Surg.Res.Commun.(in press). (1995)
• [Publications] S.Saito: "Hepatocyte growth factor promotes the growth of cytotrophoblasts by the paracrine system." J.Biochem.(in press). (1995)
• [Publications] T.Nakamura: "Hepatocyte growth factor as mitogen,motogen and morphosgen,and its roles in organ regeneration." Princeton Scientific Pub lishing Co.Inc., 19 (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 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." Springer Verlag, 14 (1994)