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Function of subendothelial basement membranes in Blood-Brain Barrier

Research Project

Project/Area Number 14370434
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionOKAYAMA UNIVERSITY

Principal Investigator

NINOMIYA Yoshifumi  Okayama Univ., Grad. Sch. of Med. & Dent., Dept. of Mol. Biol. & Biochem., Professor, 大学院・医歯学総合研究科, 教授 (70126241)

Co-Investigator(Kenkyū-buntansha) HIROHATA Satoshi  Okayama Univ., Grad. Sch. of Med. & Dent., Dept. of Mol. Biol. & Biochem., Assistant Professor, 大学院・医歯学総合研究科, 助手 (90332791)
OOHASHI Toshitaka  Okayama Univ., Grad. Sch. of Med. & Dent., Dept. of Mol. Biol. & Biochem., Instructor, 大学院・医歯学総合研究科, 講師 (50194262)
YONEZAWA Tomoko  Okayama Univ., Grad. Sch. of Med. & Dent., Dept. of Mol. Biol. & Biochem., Assistant Professor, 大学院・医歯学総合研究科, 助手 (30304299)
OHTSUKA Aiji  Okayama Univ., Grad. Sch. of Med. & Dent., Dept. of Human Morphology, Associate Professor, 大学院・医歯学総合研究科, 助教授 (50168986)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2003: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2002: ¥9,900,000 (Direct Cost: ¥9,900,000)
Keywordsbasement membrane / capillary / endothelial cell / type IV collagen / astrocyte
Research Abstract

We report the molecular cloning of a new member of the transmembrane-type immunoglobulin superfamily and designate the encoded protein as limitrin since it selectively localized to glia limitans in mouse brain. Limitrin cDNA was obtained using a subtractive hybridization procedure designed to identify molecules responsible for blood-brain barrier function. Western blots using a limitrin-specific antibody demonstrated that the gene product is expressed significantly in mouse brain and primary murine astrocytes, and is distributed in the plasma membrane. Immunohistochemical studies using confocal and electron microscopy clearly demonstrated highly polarized localization in astroglial endfeet in the perivascular region and under the pia mater in vivo. Limitrin is expressed in spinal cord and many areas of the brain but not in the median eminence or subfornical organ (the circumventricular organs) where the blood-brain barrier is lacking. Disruption of the blood-brain barrier by cold injury resulted in a drastic reduction in limitrin expression. Furthermore, during retrieval from cold injury the increased expression of limitrin in perivascular endfeet correlated with the recovery of angiogenesis in capillaries within the lesion margins. Our results suggest that limitrin is physically and functionally associated with the blood-brain barrier, implying that this protein may be useful as a diagnostic determinant of barrier integrity.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (37 results)

All Other

All Publications (37 results)

  • [Publications] Oohashi T: "Brall, a Brain-Specific Link Protein, Colocalizing with the Versican V2 Isoform at the Nodes of Ranvier in Developing and Adult Mouse Central Nervous Systems."Mol Cell Neurosci. 19・1. 43-57 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Furumatsu T: "Human chondrosarcoma secretes vascular endothelial growth factor to induce tumor angiogenesis and stores basic fibroblast growth factor for regulation of its own growth"Int J Cancer. 97・3. 313-322 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tomono Y: "Epitope-defined monoclonal. antibodies against multi plexin collagens demonstrate that type XV and XVIII collagens are expressed in specialized basement membranes"Cell Struct Function. 27・1. 9-20 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Urabe N: "Basement membrane type IV collagen molecules in the choroid plexus, pia mater and capillaries in the mouse brain."Arch Histol Cytol. 65. 133-143 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Feng K: "All four members of the Ten-m/Odz family of transmembrane proteins form dimers."J Biol Chem. 277. 26128-26135 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Borza DB: "Goodpasture autoantigen, the α3(IV) chain of collagen IV : Sequestration of two cryptic autoepitopes by intra-protomer interactions with the α4 and α5 NCl domains"J Biol Chem. 277. 40075-40083 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Chen L: "Distribution of the Collagen IV Isoforms in Human Bruch's Membrane."British J Ophtalmol. 87・2. 212-215 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Harvey SJ: "Transfer of α5(IV) collagen chain gene to smooth muscle restores in vivo expression of the α6(IV) chain in a canine model of Alport syndrome"Am J Pathol. 162. 873-885 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Zhou XH: "Ten-m/Odz genes show distinct but overlapping expression patterns during development and in adult brain."Gene Expr Patterns. 3・4. 397-405 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yonezawa T: "Limitrin, a Novel Immunoglobulin Superfamily Protein Localized to Glia Limitans Formed by Astrocyte Endfeet."Glia. 44・3. 190-204 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nomoto H: "Cloning of a Novel Transmembrane Protein MOLT Expressed by Mature Oligodendrocytes."J.Biochem. 134. 231-238 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Bekku Y: "Molecular cloning of Bral2,a novel brain-specific link protein, and immunohistochemical colocalization with brevican in perineuronal nets."Mol Cell Neurosci. 24・1. 148-159 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okazaki, Ninomiya, Friedman, Tanikawa: "Extrecellular Matrix and the Liver -Approach to Gene Therapy-"Academic Press. 467 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Oohashi T et al.: "Bral1, a Brain-Specific Link Protein, Colocalizing with the Versican V2 Isoform at the Nodes of Ranvier in Developing and Adult Mouse Central Nervous Systems."Mol Cell Neurosci. 19・1. 43-57 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Furumatsu T et al.: "Human chondrosarcoma secretes vascular endothelial growth factor to induce tumor angiogenesis and stores basic fibroblast growth factor for regulation of its own growth."Int J Cancer. 97・3. 313-322 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tomono Y et al.: "Epitope-defined monoclonal antibodies against multiplexin collagens demonstrate that type XV and XVIII collagens are expressed in specialized basement membranes."Cell Struct Function. 27・1. 9-20 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Urabe N et al.: "Basement membrane type IV collagen molecules in the choroid plexus, pia mater and capillaries in the mouse brain."Arch Histol Cytol. 65. 133-143 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Feng K et al.: "All four members of the Ten-m/Odz family of transmembrane proteins form dimers."J Biol Chem. 277. 26128-26135 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Borza DB et al.: "Goodpasture autoantigen, the α3(IV) chain of collagen IV : Sequestration of two cryptic autoepitopes by intra-protomer interactions with the α4 and α5 NC1 domains."J Biol Chem. 277. 40075-40083 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Chen L et al.: "Distribution of the Collagen IV Isoforms in Human Bruch's Membrane."British J Ophtalmol. 87・2. 212-215 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Harvey SJ et al.: "Transfer of α5(IV) collagen chain gene to smooth muscle restores in vivo expression of the α6(IV) chain in a canine model of Alport syndrome."Am J Pathol. 162. 873-885 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Zhou XH et al.: "Ten-m/Odz genes show distinct but overlapping expression patterns during development and in adult brain."Gene Expr Patterns. 3・4. 397-405 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yonezawa T et al.: "Limitrin, a Novel Immunoglobulin Superfamily Protein Localized to Glia Limitans Formed by Astrocyte Endfeet."Glia. 44・3. 190-204 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nomoto H et al.: "Cloning of a Novel Transmembrane Protein MOLT Expressed by Mature Oligodendrocytes."J.Biochem.. 134. 231-238 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Bekku Y et al.: "Molecular cloning of Bral2, a novel brain-specific link protein, and immunohistochemical colocalization with brevican in perineuronal nets."Mot Cell Neurosci. 24・1. 148-159 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Chen L: "Distribution of the Collagen IV Isoforms in Human Bruch's Membrane."British J Ophtalmol. 87・2. 212-215 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Harvey SJ: "Transfer of a5(IV) collagen chain gene to smooth muscle restores in vivo expression of the a6(IV) chain in a canine model of Alport syndrome."Am J pathol. 162. 873-885 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Zhou XH: "Ten-m/Odz genes show distinct but overlapping expression patterns during development and in adult brain."Gene Expr Patterns. 3・4. 397-405 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yonezawa T: "Limitrin, a Novel Immunoglobulin superfamily Protein Localized to Glia Limitans Formed by Astrocyte Endfeet."Glia. 44・3. 190-204 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nomoto H: "Cloning of a Novel Transmembrane Protein M0LT Expressed by Mature Oligodendrocytes."J.Biochem. 134. 231-238 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Bekku Y: "Molecular cloning of Bral2, a novel brain-specific link protein, and immunohis ochemical colocalization with brevican in perineuronal nets."Mol Cell Neurosci. 24・1. 148-159 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Oohashi T: "Bral1, a Brain-Specific Link Protein, Colocalizing with the Versican V2 Isoform at the Nodes of Ranvier in Developing and Adult Mouse Central Nervous Systems"Mol Cell Neurosci. 19・1. 43-57 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Furumatsu T: "Human chondrosarcoma secretes vascular endothelial growth factor to induce tumor angiogenesis and stores basic fibroblast growth factor regulation of its own growth"Int J Cancer. 97・3. 313-322 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tomono Y: "Epitope-defined monoclonal antibodies against multiplexin collagens demonstrate that type XV and XVIII collagens are expressed in specialized basement membranes"Cell Struct Function. 27・1. 9-20 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Urabe N: "Basement membrane type IV collagen molecules in the choroid plexus, pia mater and capillaries in the mouse brain"Arch Histol Cytol. 65. 133-143 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Feng K: "All four members of the Ten-m/Odz family of transmembrane proteins form dimers"J Biol Chem. 277. 26128-26135 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Borza DB: "Goodpasture autoantigen, the α3(IV) chain of collagen IV : Sequestration of two cryptic autoepitopes by intra-protomer interactions with the α4 and α5 NC1 domains"J Biol Chem. 277. 40075-40083 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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