細胞接着因子の機能シグナルの解析とその臨床応用を目指す総合的研究

1992 Fiscal Year Annual Research Report

• Project/Area Number: 03305001
• Research Institution: The University of Tokyo
• Principal Investigator: 林 利彦 東京大学, 教養学部, 教授 (60090528)
• Co-Investigator(Kenkyū-buntansha): 中村 敏一 九州大学, 理学部, 教授 (00049397) ; 関口 清俊 大阪府立母子保健総合医療センター, 研究所, 研究所長 (50187845) ; 永田 和宏 京都大学, 胸部疾患研究所, 教授 (50127114) ; 斉藤 佑尚 東京工業大学, 生命理工学部, 助教授 (30134810) ; 畑 隆一郎 東京医科歯科大学, 難治疾患研究所, 助手 (10014276)
• Keywords: 細胞接着 / 細胞外マトリックス / コラーゲン / ラミニン / フィブロネクチン / コンドロイチン硫酸 / ビトロネクチン / シャペロン

Research Abstract

平成4年12月19日(土)、東京大学教養学部において本研究班の成果の一端を公開シンポジウムにて公表した。参加者は約150名でほとんどは朝9時すぎから夕方4時30分過ぎまで出席し、幅広く、また場合によっては極めて具体的な突っ込んた質問・議論があり、参加者に対するアンケートの結果も好評であった。研究分担者名と講演内容を以下に述べる。赤池:新しい多機能型人工基質による肝細胞の接着制御、畑:ECM接着によるビタミンA貯蔵細胞(星細胞)の機能制御、久保木:増殖分化因子の作用発現におけるマトリックスの機能、岡山:宿主の間質応答は転移に抑制的に作用するか、関口:RGD依存性インテグリンのリガンド結合特異性の解析、永井:ヒトラミニン分子の構造と機能の多様性、松本:ビトロネクチンの糖鎖、永田:コラーゲン特異的分子シャペロンHSP47、新海:新しい結合組織成分-45KD蛋白質-、北川:基底膜成分の会合に関与するシャペロニン、斉藤:フォンビルブランド因子プロポリペプチドの新規生物活性、矢追:フィブロネクチン-FGF組み換え蛋白質の細胞増殖促進作用、吉里:線維芽細胞によるコラーゲン線維の認識機構、大山:牛大動脈に含まれるコラーゲン/プロテオグリカン複合体線維と平滑筋細胞接着、坂倉:細胞外マトリックスによる細胞接着と脱着の制御、木全:コンドロイチン硫酸による細胞接着抑制機構の解析であった。さらに、本研究班以外の関連分野の参加者(鈴木信太郎博士)のアドホックの追加講演もあった。口演しなかった班員な中には他の研究会等で本研究成果の一部を公開構演した(第65回日本生化学会シンポジウム、福岡市内中村学園大学にて)。さらに、平成5年3月22日および23日には大阪大学蛋白質研究所主催のセミナーで何人かの研究分担者が本研究の成果の一部を公開講演されると期待されている。

Research Products

• [Publications] J.Kino,E.Adachi,T.Yoshida,C.Asamatsu,K.Nakajima,K.Yamamoto,T.Hayashi: "A Novel Chain of Basement Membrane-associated Collagen as Revealed by Biochemical and Immunohistochemical Characterization of the Epitope Recogniaed by aMonoclonal Antibody Against Human Placenta Basement Membrane Collagen" Am.J.Pathology. 138. 911-920 (1991)
• [Publications] M.Yamato,K.Yamamoto,T.Hayashi: "Decrease in cellular potential of collagen gel contraction dueto in vitro cellular aging:a new aging index of fibroblasts with high sensitivity" Connective Tissue. 24. 157-162 (1992)
• [Publications] M.Yamato,K.Yamamoto,T.Hayashi: "Age-related chayges in collagen gel contraction by cultured human lungfibroblasts resulting in cross-over of contraction curves between young and aged cells" Mechanism of aging and Development. (1993)
• [Publications] M.Tsunenaga,T.Nishiyama,I.horii,Y.Nakayama,K.Arai,T.hayashi: "Effect of hyaluronate on physicochemical and biological properties of collagen solution which could be used as collagen filler" Connective Tissue Research. 28. 113-123 (1992)
• [Publications] T.Yoshida,E.Adachi,O.Matsubara,K.Nakajima,T.Hayashi: "Semiquaytitative analysis of the effects of fixation and paraffin embedding on immunoreactivity of renal basement membranes to a monoclonal antibody against type IV collagen" Arch.Histol.Cytol.55. 497-502 (1992)
• [Publications] H.Makino,T.Haramoto,K.Shikata,K.Hirata,J.Wada,S.Morioka,Z.Ota,T.Yoshida,T.Hayashi: "Distribution of a Novel Chain of Basement Membrane Associated Collagen in the Renal Tissue" Connecteve Tissue. 24. 163-168 (1992)
• [Publications] T.Nishiyama,M.Tsunenaga,N.Akutsu,I.Horii,Y.Nakayama,E.Adachi,M.Yamato and T.Hayashi: "Dissociation of Actin Actin Microfilament Organization from Acquisition and Maintenance of Elongate Shape of Human Dermal Fibroblasts in Three-Dimesional Collagen Gel" Matrix,Collagen and Related Research. 13. (1993)
• [Publications] 林 利彦: "細胞培養床としてのゲル" 表面. 30. 713-724 (1992)
• [Publications] 林 利彦: "新しいコラーゲン蛋白について" 細胞. 24. 372-377 (1992)
• [Publications] 林 利彦: "細胞外基質の三次元構造と細胞応答性" 生物物理. 32. 43-47 (1992)
• [Publications] 林 利彦: "細胞外マトリックスとその生物学的機能" 蛋白質核酸酵素. 37. 2269-2278 (1992)
• [Publications] 林 利彦: "特集によせて-細胞外マトリックスと接着因子-" 組織培養. 19. (1993)
• [Publications] 大和 雅之,林 利彦: "マトリックス構築と細胞機能制御:循環する相互作用" 組織培養. 19. (1993)
• [Publications] Yamada,S.,Koji,T.,Hata,R.,Hirohashi,S.,Kurata,S.,Senoo,H.,Sakakibara,K.,Hayashi,T.,Nakane,P.N.: "Simultaneous Expression of Type I Procollagen mRNA and Albunin in Cirrhotic Human Liver" J.Clin.Lab.Anal.66. 351-358 (1992)
• [Publications] Hata,R.and Senoo,H.: "Extracellular Matrix Regulates Cell Growth,Tissue Formation,and Cellular Functions" Tiss.Cult.Res.Commun.11. 337-343 (1992)
• [Publications] Kurata,S.,Senoo,H.,Hata,R.: "Transcriptional Activation of Type I Collagen Genes by Ascorbic Acid 2-phosphate in Human Skin Fibroblasts and Its Failure in Cells from A Patient with α2(I)-Chain-Defective Ehlers-Danlos Syndrome." Exptl.Cell Res.(1993)
• [Publications] T.Usui,T.Fujisawa,J.Takagi,and Y.Saito: "Propolypeptide and mature portions of von Willebrand factor of bovine origin recognize different sites on type-I collagen obtained from bovine tendon." European Journal of Biochimistry. 205. 363-367 (1992)
• [Publications] J.Takagi,H.Asai,and Y.Saito: "Acollagen/gelatin-binding decapeptide derived from bovine propolypeptide of von Willebrand factor." Biochemistry. 31. 8530-8534 (1992)
• [Publications] K.Hashimoito,F.Sekiya,J.Takagi,T.Tsukada,F.Sato,and Y.Saito: "Activation of phospholipases in platelets by polyclonal antibodies against a surface protein." Biochimica et Biophysica Acta. 1165. 27-31 (1992)
• [Publications] K.Ichihara,Tanaka 他: "Matrix assembly of recombinant fibronectin polypeptide consisting of amino-terminal 70 kDa and carboxyl-terminal 37 kDa regions" FEBS letters. 299. 155-158 (1992)
• [Publications] K.Hashino 他: "Eygineering of Artificial Cell Adhesion Proteins by Grafting the Arg-Gly-Asp Cell Adhesive Signal to a Calpastatin Segment" J.Biochem.112. 547-551 (1992)
• [Publications] T.Maeda 他: "Engineering of artificial cell-adhesive proteins by grafting EILDVPST sequence derived from fibronectin" J.Biochem.113. 29-35 (1993)
• [Publications] F.Oyama 他: "Coordinate oncodevelopmental modulation of alternative splicing of fibronectin pre-mRNA at ED-A,ED-B,and CS1 regions in human liver tumors" Cancer Research.
• [Publications] H.Takechi 他5名: "Molecular cloning of a mouse 47-kDa heat-shock protein (HSP47),a collagen-binding stress protein." European Journal of Biochemistry. 206. 323-329 (1992)
• [Publications] A.NAKAI 他3名: "Involvement of the stress protein HSP47 in procollagen processing in the eudoplasmic reticulumn." Journal of cell Biology. 117. 903-914 (1992)
• [Publications] M.KOISHI 他7名: "Quercetin,an inhibitor of heat shock protein syuthesis, in hibits the acquisition of thermotolerance in a human colon cancer cell line." Japanese Journal of Concer Research. 83. 1216-1222 (1992)
• [Publications] N.KIOKA 他5名: "Quercetin,a bioflavonoids,inhibits the increasc of human mu Hidvug resistance gene(MDRI)expression caused by arsenite." FEBS Letters. 301. 307-309 (1992)
• [Publications] T.SAKATA 他9名: "Constitutire expression of Leukemio inhibitory factor(LIF)mRNA and Production of LIF by a Cloned murine thymic stronal cdllne." Thymus. 19. 89-95 (1992)
• [Publications] M.YAMAGUCHI 他5名: "Down-regulation of interleukin 6 receptors of mouse myelomonocytic leukemic cells by lieukemia inhibitory factor." Journal of Biological chemistry. 267. 22035-22042 (1992)
• [Publications] N.NAKAMURA 他3名: "Purificetion and characterization of avinentin-specific protease in monsc myeloid leukenia cells." European Jourual of Biochenistry. 205. 947-954 (1992)
• [Publications] N.HOSOKAWA 他6名: "Inhibition of the actiration of heat shock factor in vivo and in vitro by rlavonoids" Molecular and Cellular Biology. 12. 3490-3498 (1992)
• [Publications] N.HOSOKAWA 他4名: "Structure of the gene encoding mouse 47-kDa heat-shock protein(HSP47)" Gene. (1993)
• [Publications] M.SATOH 他4名: "Modulation of the phosphorylation of glucose-regulated protein GRP78,by trausformation and inhibitiron of glycosylation." Experimental Cell Research. (1993)
• [Publications] S.NISHI 他7名: "Ischemic tolerance due to the induction of HSP70 in a rat ischemic recirculation model." Brain.Research. (1993)
• [Publications] G.Shiota,D.B.Rhoads,T.C.Wang,T.Nakamura and E.V.Schmidt: "Hepatocyte growth factor 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 destribution of hepatocyte growth factor receptor and its exclusive dowy-regulation in aregenerating 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 of 1,2-diacylglycerol via phosphatidylcholine-phospholipase C in cul-tured 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:downregu-Lation 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 vareous cell species." Exp.Cell Res.202,. 423-431 (1992)
• [Publications] M.Hamanoue,K.Kaoaeda,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 gigh 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 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: "Roleof the adenylate cyclase,phosphoinositidase c and receptor tyrosine Kinase system in the control of hcpatocyte 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 factofor 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-1 in MDCK epithelial cells." J.Biol.Chem.267,. 20493-20496 (1992)
• [Publications] M.Masuhara,S.L.Katyal,T.Nakamura and H.Shinozuka: "Differential expression of hepatocyte growth factor,transforming growth factor-alpha and transforming growth factor-betal mRNAs in two experimental models of liver cell proliferation." Hepatology,. 16,. 1241-1249 (1992)
• [Publications] K.Matsumoto,H.Ttajima,H.Okazaki,and T.Nakamura: "Negative regulation of hepatocyte growth factor gene expression in human lung fibroblasts and leukemic cells by transforming growth factor-β1 and 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.Bodescot,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] T.Hayashi,T.Nishiyama,E.Adachi: "Collagen as a Potent Regulator for Cellular Activety --Collagen Matrix-to-Cell Contact Inhibition Fundamental Invetigations on the Creation of Biofunctional Materials,Ed.by S.Okamura,T.Tsuruta,Y.Imanishi,J.Sunamoto," KAGAKU-DOJIN,Kyoto, 54-64 (1991)
• [Publications] 林 利彦: "ヒトの体は再生できるか" マグロウヒル出版株式会社東京, 190 (1991)
• [Publications] 大和 雅之,林 利彦: "コラーゲンゲル内培養新生化学実験講座6日本生化学会編" 東京化学同人東京, 309-312 (1992)
• [Publications] 林 利彦,田中 静子: "結合組織,生化学臓器と免疫各論I、辻孝夫編、" 文永堂出版, 377-419 (1992)
• [Publications] 大和 雅之,林 利彦: "細胞増殖と細胞外マトリックス・接着因子細胞成長因子partIII" 朝倉書店東京, (1993)
• [Publications] 林 利彦: "マトリックスの構造と機能肝疾患の最近進歩VII," メディカルレビュー社、大阪, (1993)
• [Publications] T.Hayashi,M.Yamato,E.Adachi,K.Yamamoto: "Unique Features of Type I Collagen as a Regulator for Fibroblast Functions:Iterative Interactions be" Elsevier Pub.Co., (1993)
• [Publications] 関口 清俊: "新生化学実験講座第6巻「生体膜と膜輸送」pp.326-331(分担執筆)" 東京化学同人, 424 (1992)
• [Publications] 松山 聡,関口 清俊: "新生化学実験講座第10巻「血管:内皮と平滑筋」§11・3・2フィブロネクチン・ビトロネクチン:遺伝子レベル" 東京化学同人,
• [Publications] K.NAGATA,他5名: "Radiation Research" W.C.Dewey他3名編Academic Press, 976-979 (1992)
• [Publications] K.NAGATA: "Hyperthermic Oncology in Japan" R.KAMADA編Shinohara Publishing Ine., 9-11 (1992)
• [Publications] K.NAGATA and N.HOSOKAWA: "Hyperthermic Oncology" T.C.Cetas and E.W.Gerner編Taylor and Francis Inc., (1993)