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Matrix metalloprotease 12 is a novel prospective molecule regulating neuropathic pain

Research Project

Project/Area Number 25861397
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Anesthesiology
Research InstitutionNational Center of Neurology and Psychiatry (2015)
Wakayama Medical University (2013-2014)

Principal Investigator

Ujiie Yuka  国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第五部, 流動研究員 (20511562)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords神経障害性疼痛 / 神経炎症 / マクロファージ / メタロプロテアーゼ / マトリックスメタロプロテアーゼ
Outline of Final Research Achievements

Neuroinflammation mediated by activated macrophages is important for pathogenesis of neuropathic pain. Here, we investigated the role of MMP12 in neuropathic pain. The gene expression of MMP12 was increased in the injured sciatic nerve (SCN), and MMP12 protein was localized on infiltrating macrophages in the injured site of SCN. By DiI labeling for peripheral blood vessels, DiI leaked into the surrounding tissue after injury, and macrophages accumulated around DiI labeled peripheral vessels. The expression of MMP12 was increased in LPS-activated macrophages. Perineural injection of macrophages depletion agent attenuated nerve injury-induced both tactile allodynia and thermal hyperalgesia, and suppressed the mRNA expressions of MMP12 and inflammatory cytokines. Furthermore, perineural injection of MMP12 specific inhibitor also suppressed tactile allodynia and thermal hyperalgesia. Taken together, MMP12 derived from macrophages acts as an exacerbating factor of neuropathic pain.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (26 results)

All 2015 2014 2013

All Journal Article (16 results) (of which Peer Reviewed: 16 results,  Acknowledgement Compliant: 6 results,  Open Access: 5 results) Presentation (10 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Exploration of novel therapeutic targets for neuropathic pain based on the regulation of immune cells.2015

    • Author(s)
      Kobayashi Y, Kiguchi N, Saika F, Kishioka S.
    • Journal Title

      Nihon Shinkei Seishin Yakurigaku Zasshi.

      Volume: 35(3) Pages: 65-72

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Macrophage-T cell interactions mediate neuropathic pain through the glucocorticoid-induced tumor necrosis factor ligand system.2015

    • Author(s)
      Kobayashi Y, Kiguchi N, Fukazawa Y, Saika F, Maeda T, Kishioka S.
    • Journal Title

      J Biol Chem.

      Volume: 290(20) Issue: 20 Pages: 12603-12613

    • DOI

      10.1074/jbc.m115.636506

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Peripheral interleukin-4 ameliorates inflammatory macrophage-dependent neuropathic pain.2015

    • Author(s)
      Kiguchi N, Kobayashi Y, Saika F, Sakaguchi H, Maeda T, Kishioka S
    • Journal Title

      Pain

      Volume: 156(4) Issue: 4 Pages: 684-93

    • DOI

      10.1097/j.pain.0000000000000097

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] TC-2559, an α4β2 nicotinic acetylcholine receptor agonist, suppresses the expression of CCL3 and IL-1β through STAT3 inhibition in cultured murine macrophages.2015

    • Author(s)
      Kiguchi N, Saika F, Kobayashi Y, Ko MC, Kishioka S.
    • Journal Title

      J Pharmacol Sci.

      Volume: 128(2) Issue: 2 Pages: 83-86

    • DOI

      10.1016/j.jphs.2015.04.009

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Macrophage-T cell interactions mediate neuropathic pain through the glucocorticoid-induced tumor necrosis factor ligand system.2015

    • Author(s)
      Kobayashi Y, Kiguchi N, Fukazawa Y, Saika F, Maeda T, Kishioka S.
    • Journal Title

      J. Biol. Chem.

      Volume: 印刷中

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Matrix metalloprotease 12 is a novel prospective molecule regulating neuropathic pain2015

    • Author(s)
      Kobayashi Y, Kishioka S.
    • Journal Title

      PAIN RESEARCH

      Volume: 30 Pages: 37-45

    • NAID

      130005061789

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Peripheral alpha4beta2 nicotinic acetylcholine receptor signalling attenuates tactile allodynia and thermal hyperalgesia after nerve injury in mice.2015

    • Author(s)
      Saika F, Kiguchi N, Kobayashi Y, Kishioka S
    • Journal Title

      Acta Physiol (Oxf)

      Volume: 213(2) Issue: 2 Pages: 462-71

    • DOI

      10.1111/apha.12437

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of physical dependence on nicotine and endogenous opioid system--participation of α7 nicotinic acetylcholine receptor2014

    • Author(s)
      Kishioka S, Kiguchi N, Kobayashi Y, Saika F, Yamamoto C.
    • Journal Title

      Nihon Arukoru Yakubutsu Igakkai Zasshi

      Volume: 49(5) Pages: 227-237

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Epigenetic regulation of CC-chemokine ligand 2 in nonresolving inflammation.2014

    • Author(s)
      Kiguchi N, Saika F, Kobayashi Y, Kishioka S
    • Journal Title

      Biomol Concepts

      Volume: 5(4) Issue: 4 Pages: 265-73

    • DOI

      10.1515/bmc-2014-0022

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nicotine Effects and the Endogenous Opioid System2014

    • Author(s)
      Kishioka S, Kiguchi N, Kobayashi Y, Saika F.
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 125 Issue: 2 Pages: 117-124

    • DOI

      10.1254/jphs.14R03CP

    • NAID

      130004438636

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] CC-Chemokine Ligand 2 Facilitates Conditioned Place Preference to Methamphetamine Through the Activation of Dopamine Systems2014

    • Author(s)
      Wakida N, Kiguchi N, Saika F, Nishiue H, Kobayashi Y, Kishioka S.
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 125 Issue: 1 Pages: 68-73

    • DOI

      10.1254/jphs.14032FP

    • NAID

      130003391520

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Vascular endothelial growth factor signaling in injured nerves underlies peripheral sensitization in neuropathic pain.2014

    • Author(s)
      Kiguchi N, Kobayashi Y, Kadowaki Y, Fukazawa Y, Saika F, Kishioka S
    • Journal Title

      J Neurochem

      Volume: 129 Issue: 1 Pages: 169-178

    • DOI

      10.1111/jnc.12614

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of endogenous opioid system located downstream of α7 nicotinic acetylcholine receptor in mice with physical dependence on nicotine.2014

    • Author(s)
      Ueno K, Kiguchi N, Kobayashi Y, Saika F, Wakida N, Yamamoto C, Maeda T, Ozaki M, Kishioka S
    • Journal Title

      J Pharmacol Sci

      Volume: 124 (1) Pages: 47-53

    • NAID

      130003382624

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Epigenetic upregulation of CCL2 and CCL3 via histone modifications in infiltrating macrophages after peripheral nerve injury.2013

    • Author(s)
      Kiguchi N, Kobayashi Y, Saika F, Kishioka S
    • Journal Title

      Cytokine

      Volume: 64 Issue: 3 Pages: 666-672

    • DOI

      10.1016/j.cyto.2013.09.019

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pharmacokinetic evidence for the long-lasting effect of nor-binaltorphimine, a potent kappa opioid receptor antagonist, in mice.2013

    • Author(s)
      Kishioka S, Kiguchi N, Kobayashi Y, Yamamoto C, Saika F, Wakida N, Ko MC, Woods JH
    • Journal Title

      Neurosci Lett

      Volume: 552 Pages: 98-102

    • DOI

      10.1016/j.neulet.2013.07.040

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] HMGB1 as a potential therapeutic target for neuropathic pain.2013

    • Author(s)
      Maeda T, Ozaki M, Kobayashi Y, Kiguchi N, Kishioka S
    • Journal Title

      J Pharmacol Sci.

      Volume: 123 (4) Pages: 301-305

    • NAID

      130003382621

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 神経障害性疼痛に及ぼすMMP12の影響2015

    • Author(s)
      雑賀史浩、氏家悠佳、木口倫一、松崎伸介、岸岡史郎
    • Organizer
      第128回日本薬理学会近畿部会
    • Place of Presentation
      千里ライフサイエンスセンター, 大阪
    • Year and Date
      2015-11-20
    • Related Report
      2015 Annual Research Report
  • [Presentation] Matrix Metalloprotease 12: Novel Target for Neuropathic Pain2015

    • Author(s)
      Kishioka S, Kobayashi Y, Kiguchi N, Saika F, Matsuzaki S.
    • Organizer
      BIT's 6th Annual WorldCongress of NeuroTalk-2015
    • Place of Presentation
      Hangzhou Blossom Water Museum Hotel, Hangzhou, China
    • Year and Date
      2015-05-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A novel therapeutic strategy for neuropathic pain through regulating peripheral immune cells2015

    • Author(s)
      Kobayashi Y, Kiguchi N, Fukazakwa Y, Saika F, Maeda T, Kishioka S
    • Organizer
      日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場, 愛知
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Research-status Report
  • [Presentation] 傷害坐骨神経周囲の新生血管網形成とマクロファージ2014

    • Author(s)
      小林 悠佳、木口 倫一、雑賀 史浩、門脇 友維、岸岡 史郎
    • Organizer
      生体機能と創薬シンポジウム2014
    • Place of Presentation
      近畿大学薬学部東大阪キャンパス、大阪
    • Year and Date
      2014-08-28 – 2014-08-29
    • Related Report
      2014 Research-status Report
  • [Presentation] ACTIVATION OF CROSSTALK BETWEEN MACROPHAGES AND T-CELLS LEADS TO NEUROPATHIC PAIN THROUGH GLUCOCORTICOID-INDUCED TNF RECEPTOR LIGAND (GITRL)-GITR PATHWAY2014

    • Author(s)
      Kobayashi Y, Kiguchi N, Saika F, Fukazawa Y, Kishioka S
    • Organizer
      9th Federation of European Neuroscience Society
    • Place of Presentation
      Milan, Italy
    • Year and Date
      2014-07-05 – 2014-07-09
    • Related Report
      2014 Research-status Report
  • [Presentation] 新規疼痛制御分子としてのマクロファージ由来マトリックスメタロプロテアーゼ12の可能性2014

    • Author(s)
      小林 悠佳、木口 倫一、岸岡 史郎
    • Organizer
      第36回日本疼痛学会
    • Place of Presentation
      KKRホテル大阪、大阪
    • Year and Date
      2014-06-20 – 2014-06-21
    • Related Report
      2014 Research-status Report
  • [Presentation] Direct evidences for a key role of macrophage specific molecule in b\nerve injury induced neuropathic pain.2014

    • Author(s)
      Kobayashi Y, Kiguchi N, Saika F, fukazawa Y, Kishioka S
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      宮城県仙台市
    • Related Report
      2013 Research-status Report
  • [Presentation] Interaction between macrophage inflammatory proteins and matrix metalloprotease 12 in macrophage is involved in neuropathic pain.2013

    • Author(s)
      Kobayashi Y, Kiguchi N, Fukazawa Y, Saika F, Kishioka S
    • Organizer
      Asian Pain Symposium 2013
    • Place of Presentation
      愛知県岡崎市
    • Related Report
      2013 Research-status Report
  • [Presentation] 慢性疼痛の病態基盤におけるマクロファージ由来matrix metalloprotease 12の役割.2013

    • Author(s)
      小林悠佳、木口倫一、雑賀史浩、岸岡史郎
    • Organizer
      第33回鎮痛薬・オピオイドペプチドシンポジウム
    • Place of Presentation
      兵庫県神戸市
    • Related Report
      2013 Research-status Report
  • [Presentation] Involvement of matrix metalloprotease 12 in pathogenesis of neuropathic pain.2013

    • Author(s)
      Kobayashi Y, Kiguchi N, Fukazawa Y, Kishioka S
    • Organizer
      第56回日本神経科学大会
    • Place of Presentation
      京都府京都市
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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