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2012 Fiscal Year Final Research Report

Critical role of KLK6 in the pathogenesis of Multiple Sclerosis

Research Project

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Project/Area Number 23700436
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurochemistry/Neuropharmacology
Research InstitutionAsahikawa Medical College

Principal Investigator

BANDO Yoshio  旭川医科大学, 医学部, 講師 (20344575)

Co-Investigator(Renkei-kenkyūsha) YOSHIDA Shigetaka  旭川医科大学, 医学部, 教授 (20230740)
Project Period (FY) 2011 – 2012
Keywords多発性硬化症 / セリンプロテアーゼ
Research Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). It results in neurological impairments. One of animal model is myelin oligodendrocyte glycoprotein (MOG)- induced experimental autoimmune encephalomyelitis (EAE), which is characterized by paralysis and immune cell infiltration in the CNS. We have previously reported that a serine protease, Kallikrein 6 (KLK6), is produced by exclusively mature oligodendrocytes in the CNS, and that KLK6 is up-regulated in oligodendrocytes after spinal cord injury and EAE. However, the function of KLK6 in the pathogenesis of MS has not been fully understood.
Here we report that KLK6 is involved in onset of EAE via BBB breakdown. To investigate the role of KLK6 in demyelination, we examined the effect of KLK6 on onset of EAE in KLK6 knock out (KO) mice. KLK6 KO mice exhibited an altered EAE progression characterized by delayed onset and progression of clinical symptoms as compared to wild-type mice. Histological study with luxol fast blue also revealed a decreased number of infiltrating inflammatory cells in spinal cord with EAE, suggesting that absence of KLK6 suppressed infiltration of peripheral inflammatory cells into the CNS with EAE. We next examined the effect of KLK6 on BBB permeability by evans blue dye injection. KLK6 KO mice showed much suppression of BBB permeability compared to wild-type mice. Finally we found that activation of Matrix metalloprotease-9 was inhibited in KLK6 KO mice with EAE. These results suggest that KLK6 play a crucial role of the pathogenesis of EAE.

  • Research Products

    (6 results)

All 2013 2012 Other

All Journal Article (3 results) Presentation (2 results) Remarks (1 results)

  • [Journal Article] Three-dimensional ultra-structures of myelin and the axons in the spinal cord: application of SEM with the osmium maceration method to the central nervous system in two mouse models.2013

    • Author(s)
      Nomura T., Bando Y., Bochimoto H., Koga D., Watanabe T., Yoshida S.
    • Journal Title

      Neuroscience Researc

      Volume: 75 Pages: 190-197

  • [Journal Article] In vivo analysis of kallikrein-related peptidase 6 (KLK6) function in oligodendrocyte development and the expression of myelin proteins2013

    • Author(s)
      Murakami K., Jiang YP., Tanaka T., Bando Y., Mitrovic B, Yoshida S.
    • Journal Title

      Neuroscience

      Volume: 236 Pages: 1-11

  • [Journal Article] Minocycline reduces remyelination by suppressing ciliary neurotrophic factor expression after cuprizone-induced demyelination.

    • Author(s)
      Tanaka T., Murakami K., Bando Y., Yoshida S.
    • Journal Title

      Journal of Neurochemistry

      Volume: (in press)

  • [Presentation] 脱髄性疾患モデルマウスを用いた脱髄機構の解析2012

    • Author(s)
      板東良雄
    • Organizer
      第14回ORIGIN神経科学研究会
    • Place of Presentation
      金沢
    • Year and Date
      20120831-0902
  • [Presentation] CNS myelin and axon morphology in demyelination and dysmyelination in mouse models2012

    • Author(s)
      Bando Y., Nomura T., Bochimoto H., Watanabe T. , Yoshida S.
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Year and Date
      20120818-0923
  • [Remarks] First three authors equally contributed to this work.

    • URL

      http://www.asahikawa-med.ac.jp/dept/mc/anato1/

URL: 

Published: 2014-09-25  

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