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Studies on a new growth factor under the control of retinoic acid, midkine (MK)

Research Project

Project/Area Number 04454594
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 物質生物化学
Research InstitutionNagoya University School of Medicine (1993)
Kagoshima University (1992)

Principal Investigator

MURAMATSU Takashi  Nagoya University School of Medicine, Department of Biochemistry, Professor, 医学部, 教授 (00030891)

Co-Investigator(Kenkyū-buntansha) MURAMATSU Hisako  Kagoshima University Faculty of Medicine, Department of Biochemistry, Research a, 医学部, 助手 (50182134)
OZAWA Masayuki  Kagoshima University Faculty of Medicine, Department of Biochemistry, Associate, 医学部, 助教授 (90136854)
松原 修一郎  鹿児島大学, 医学部, 助手 (60199841)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1993: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1992: ¥4,300,000 (Direct Cost: ¥4,300,000)
KeywordsMidkine / MK gene / Growth factor / neurotrophic factor / retinoic acid receptor / Syndecan / Arzheimer disease / Wilms'tumor / MK / ヘパリン / レチノイン酸 / ヒト癌
Research Abstract

The arrangement of -S-Sbridges in MK was determined as follows : C_<12>-C_<36>, C_<20>-C_<45>, C_<27>-C_<49>, C_<54>-C_<91>, C_<69>-C_<101>, indicating that MK is composed of two domains. The 2kb upstream sequence of mouse MK gene (MK2 type) was linked to CAT gene and transfected to F9 cells. The 2kd sequence mediated CAT gene activation upon retinoic acid treatment. A retinoic acid responsive enhancer was found in the 2kb fragment. The core element has high dergee of homology to retinoic acid receptor binding sequence, and indeed bound to RXR・RAR heterodimer. MK had neurotrophic activity to various embryonic neurons such as from spinal cord and dorsal root ganglion. MK bound to syndecan and to a putative MK receptor of 85 kDa. MK expression was increased in many human carcinomas including Wilm's tumor, hepatocellular carcinoma and pancreatic carcinoma. Senile plaqule in the brain of Arzheimer disease patients invariable expressed MK.As above, MK is an important growth factor under the control of retinoic acid, and is probably involved in ethiology of human diseases.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Tsutsui,J.,Kadomatsu,K.,Matsubara,S.,Nakagawara,A.,Hamanoue,M.,Takao,S.,Shimazu,H.,Ohi,Y.and Muramatsu,T.: "A new family of heparin-binding growth differentiation factors:increased midkine expression in Wilms' tumor and other human carcinomas" Cancer Research. 53. 1281-1285 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Fabri,L.,Maruta,H.,Muramatsu,H.,Muramatsu,T.,Simpson,R.J.,Burgess,A.W.and Nice,E.C.: "Structural characterization of native and recombinant forms of the neurotrophic cytokine MK" J.Chromatog.646. 213-226 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kitamura,M.,Shirasawa,T.,Mitarai,T.,Muramatsu,T.and Maruyama,N.: "A retinoid responsive cytokine gene,MK,is preferentially expressed in the proximal tubules of the kidney and human tumor cell lines" Am.J.Pathol.142. 425-431 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kaname,T.,Kuwano,A.,Murano,I.,Uehara,K.,Muramatsu,T.and Kajii,T.: "Midkine gene(MDK),a gene for prenatal differentiation and neuroregulation,maps to band 11p11.2 by fluorescence in situ hybridization" Genomics. 17. 514-515 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Michikawa,M.,Kikuchi,S.,Muramatsu,H.,Muramatsu,T.and Kim,S.U.: "Retinoic acid responsive gene product,midkine(MK),has neurotrophic functions for mouse spinal cord and dorsal root ganglion neurons in culture" J.Neurosci.Res.35. 530-539 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yasuhara,O.,Muramatsu,H.,Kim,S.U.,Muramatsu,T.,Maruta,H.and McGeer,P.L.: "Midkine,a novel neurotrophic factor,is present in senile plaques of Alzheimer disease" Biochem.Biophys.Res.Commun.192. 246-251 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Satoh,J.,Muramatsu,H.,Moretto,G.,Muramatsu,T.,Chang,H.J.,Kim,S.T.,Cho,J.M.and Kim,S.U.: "Midkine that promotes survival of human neurons is produced by fetal human astrocytes in culture" Dev.Brain Res.75. 201-205 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Muramatsu,H.,Shirahama,H.,Yonezawa,S.,Maruta,H.and Muramatsu,T.: "Midkine(MK),a retinoic acid-inducible growth/differentiation factor:immunochemical evidence for the function and distribution" Dev.Biol.159. 392-402 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tsutsui, J., Kadomatsu, K., Matsubara, S., Nakagawara, A., Hamanoue, M.takao, S., Shimazu, H., Ohi, Y.and Muramatsu, T.: "A new family ofheparin-binding growth defferentiation factors : increased midkine expression in Wilms'tumor and other human carcinomas" Cancer Res.53. 1281-1285 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Fabri, L., Maruta, H., Muramatsu, H., Muramatsu, T., Simpson, R.J., Burgess, A.W.and Nice, E.C.: "Structural characterization of native and recombinant forms of the neurotrophic cytokine MK" J.Chromatog.646. 213-226 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kitamura, M., Shirasawa, T., Mitarai, T., Muramatsu, T.and Maruyama, N.: "A retinoid responsive cytokine gene, MK, is preferantially expressed in the proximal tubules of the kidney and human tumor cell lines" Am.J.Pathol.142. 425-431 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kaname, T., Kuwano, A., Murano, I., Uehara, K., Muramatsu, T.and Kajii, T.: "Midkine gene (MDK), a gene for prenatal differentiation and neuroregulation, maps to band 11p11.2 by fluorescence in situ hydridization" Genomics. 17. 514-515 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Michikawa, M., Kikuchi, S., Muramatsu, H., Muramatsu, T.and Kim, S.U.: "Retinoic acid responsive gene product, midkine (MK), has neurotrophic functions for mouse spinal cord and dorsal root ganglion neurons in culture" J.Neurosci.Res.35. 530-539 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yasuhara, O., Muaramatsu, H., Kim, S.U., Muramatsu, T., Maruta, H.and McGeer, P.L.: "Midkine, a novel neurotrophic factor, is present in senile plaques of Alzheimer disease" Biochem.Biophys.Res.Commun.192. 246-251 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Satoh, J., Muramatsu, H., Moretto, G., Muramatsu, YT., Chang, H.J., Kim, S.T., Cho, J.M.and Kim, S.U.: "Midkine that promotes survival of human neurons is produced by fetal human astrocytes in culture" Dev.Brain Res.75. 201-205 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Muramatsu, H., Shirahama, H., Yonezawa, S., Maruta, H.and Muramatsu, T.: "Midkine (MK) a retinoic acid-inducible growth/differentiatin factor : Immunochenical evidence for the function and distribution" Dev.Biol. 159. 392-402 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tsutsui,J.,Kadomatsu,K.,Matsubara,S.,Nakagawara,A.,Hamanoue,M.,Takao,S.,Shimazu,H.,Ohi,Y.and Muramatsu,T.: "A new family of heparin-binding growth differentiation factors:increased midkine expression in Wilms'tumor and other human carcinomas" Cancer Research. 53. 1281-1285 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Fabri,L.,Maruta,H.,Muramatsu,H.,Muramatsu,T.,Simpson,R.J.,Burgess,A.W.and Nice,E.C.: "Structural characterization of native and recombinant forms of the neurotrophic cytokine MK" J.Chromatog.646. 213-226 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kitamura,M.,Shirasawa,T.,Mitarai,T.,Muramatsu,T.and Maruyama,N.: "A retinoid responsive cytokine gene,MK,is preferentially expressed in the proximal tubules of the kidney and human tumor cell lines" Am.J.Pathol.142. 425-431 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kaname,T.,Kuwano,A.,Murano,I.,Uehara,K.,Muramatsu,T.and Kajii,T.: "Midkine gene(MDK),a gene for prenatal differentiation and neuroregulation,maps to band 11p11.2 by fluorescence in situ hybridization" Genomics. 17. 514-515 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Michikawa,M.,Kikuchi,S.,Muramatsu,H.,Muramatsu,T.and Kim,S.U.: "Retinoic acid responsive gene product,midkine(MK),has neurotrophic functions for mouse spinal cord and dorsal root ganglion neurons in culture" J.Neurosci.Res.35. 530-539 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yasuhara,O.,Muramatsu,H.,Kim,S.U.,Muramatsu,T.,Maruta,H.and McGeer,P.L.: "Midkine,a novel neurotrophic factor,is present in senile plaques of Alzheimer disease" Biochem.Biophys.Res.Commun.192. 246-251 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Satoh,J.,Muramatsu,H.,Moretto,G.,Muramatsu,T.,Chang,H.J.,Kim,S.T.,Cho,J.M.and Kim,S.U.: "Midkine that promotes survival of human neurons is produced by fetal human astrocytes in culture" Dev.Brain Res.75. 201-205 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Muramatsu,H.,Shirahama,H.,Yonezawa,S.,Maruta,H.and Muramatsu,T.: "Midkine(MK),a retinoic acid-inducible growth/differentiation factor:immunochemical evidence for the function and distribution" Dev.Biol.159. 392-402 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Uehara,K.: "Genomic structure of human midkine(MK),a retinoic acidresponsive growth/differentiation factor" J.Biochem.111. 563-567 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nakamoto,M.: "A new family of heparin binding growth/differentiation factors:defferential expression of the midkine (MK) and HB-GAM genes during mouse embryogenesis" J.Biochem.112. 346-349 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kaname,T.: "Midkine gene (MDK),a gene for prenatal differentiation and neuroregulation,maps to band 11p11.2 by fluorescence in situ hybridization" Genomics. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Maruta,H.: "Midkine (MK) a retinoic acid (RA)-inducible gene product produced in E.Coli acts on neuronal and HL-60 cells" Growth Factors. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Michikawa,M.: "Retinoic acid responsive gene product,midkine (MK) has neurotrophic functions for muose spinal cord and dorsal root ganglion neurons in culture" J.Neurosci.Res.(1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Tsutsui,J.: "A new family of heparin-binding growth/differentiation factors:increased midkine expression in Wilms' tumor and other human carcinomas" Cancer Res.(1993)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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