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細菌感染症の転帰を決める細胞ロジスティクス機構の分子基盤解析

Publicly

Project AreaIntracellular logistics: interdisciplinary approaches to pathophysiology of membrane traffic
Project/Area Number 23113715
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionOsaka University

Principal Investigator

天野 敦雄  大阪大学, 歯学研究科(研究院), 教授 (50193024)

Project Period (FY) 2011-04-01 – 2013-03-31
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2012: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2011: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywordsメンブレントラッフィク / オートファジー / 歯周病菌 / 感染 / 歯学 / 細菌感染 / 細胞・組織 / メンブレントラフィック / SNARE
Outline of Annual Research Achievements

歯周病菌は歯肉上皮細胞や歯肉繊維芽細胞に侵入し、感染の進行と慢性化を図る。一方、宿主細胞はエンドサイトーシス経路などのメンブレントラフィック機構を用いて侵入細菌を分解する。この「細菌 vs メンブレントラフィック」の戦いの転機が歯周病の発症において大きな影響を与えている。
メンブレントラフィック機構のひとつであるオートファジー(自食作用)とは、細胞の中を掃除することで病気が起こるのを防ぐ仕組である。細胞の中に壊れたミトコンドリアや古いタンパク質などが溜まったり病原体が侵入したりすると、細胞の健康が損なわれ、その結果アルツハイマー病、発がん、心不全、糖尿病、感染症、炎症など多岐にわたる病気が起こる。それを防ぐために細胞はオートファジーという仕組みを持っている。オートファジーを担うオートファゴソームは、膜で包まれた球形のオルガネラであり、必要に応じて細胞の中に現れ、細胞にとって有害な上述のものを取り込んで分解する働きを持つ清掃マシーンのような存在である。どこからともなく現れ役目を終えると消えるため、どこで造られているのかがこれまで40年近く論争の的になっていた。
最も強力な歯周病菌でもあるP. gingivalis は細胞質内へと侵入しオートファジーにより捕獲され分解・殺菌される。我々はオートファゴソームの形成起源について検討を加えた。その結果、オートファゴソームが別のオルガネラであるミトコンドリアと小胞体が接触する場所で造られていることを見出した。さらに、歯周病菌は細胞のリサイクリング経路をハイジャックすることにより細胞外に脱出し、隣接細胞に再侵入することにより組織内での感染を拡大させていることも明かとした。

Research Progress Status

24年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

24年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2012 Annual Research Report
  • 2011 Annual Research Report

Research Products

(51 results)

All 2013 2012 2011

All Journal Article Presentation Book

  • [Journal Article] Porphyromonas gingivalis fimbriae2013

    • Author(s)
      Enersen M
    • Journal Title

      Journal of Oral Microbiology

      Volume: 印刷中

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of periodontal biofilm in Down syndrome patients: a comparative study2013

    • Author(s)
      Martinez-Martinez RE
    • Journal Title

      Journal of Medical Microbiology

      Volume: 印刷中

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genotype analysis of Porphyromonas gingivalis fimA in Korean adults using new primers2013

    • Author(s)
      Moon JH
    • Journal Title

      Journal of Medical Microbiology

      Volume: 印刷中

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The serine phosphatase SerB of Porphyromonas gingivalis suppresses IL-8 production by dephosphorylation of NF-κB RelA/p65.2013

    • Author(s)
      Takeuchi H, Hirano T, Whitmore SE, Morisaki I, Amano A, Lamont RJ
    • Journal Title

      PLoS Pathogen

      Volume: 9(4) Pages: 1-13

    • DOI

      10.1371/journal.ppat.1003326

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autophagosomes form at ER–mitochondria contact sites2013

    • Author(s)
      Hamasaki M, Furuta N, Matsuda A, Nezu A, Yamamoto A, Fujita N, Oomori H, Noda T, Haraguchi T, Hiraoka Y, Amano A, Yoshimori T
    • Journal Title

      Nature

      Volume: 495 Pages: 389-393

    • DOI

      10.1038/nature11910

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification and characterization of Porphyromonas gingivalis client proteins that bind to2013

    • Author(s)
      Maeda K, Nagata H, Kuboniwa M, Ojima M, Osaki T, Minamino N, Amano A
    • Journal Title

      Infection and immunity

      Volume: 81(3) Pages: 753-63

    • DOI

      10.1128/iai.00875-12

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Distribution and molecular characterization of Porphyromonas gulae carrying a new fimA genotype2012

    • Author(s)
      Yamasaki Y, Nomura R, Nakano K, Inaba H, Kuboniwa M, Hirai N, Shirai M, Kato Y, Murakami M, Naka S, Iwai S, Matsumoto-Nakano M, Ooshima T, Amano A, Asai F
    • Journal Title

      Veter inar y Microbiology

      Volume: 161(1) Pages: 196-205

    • DOI

      10.1016/j.vetmic.2012.07.026

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of signaling pathways mediating cell cycle arrest and apoptosis induced by2012

    • Author(s)
      Inaba H, Kuboniwa M, Sugita H, Lamont RJ, Amano A
    • Journal Title

      Infection and immunity

      Volume: 80(8) Pages: 2847-2857

    • DOI

      10.1128/iai.00258-12

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Insights into the virulence of oral biofilms2012

    • Author(s)
      Kuboniwa M, Tribble GD, Hendrickson EL, Amano A, Lamont RJ, Hackett M
    • Journal Title

      discoveries from proteomics. Exper t Review of Proteomics

      Volume: 9(3) Pages: 311-23

    • DOI

      10.1586/epr.12.16

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Negative regulation of Odd-skipped related 2 by TGF-beta achieves the induction of cellular2012

    • Author(s)
      Kawai S, Amano A
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 421(4) Pages: 696-700

    • DOI

      10.1016/j.bbrc.2012.04.064

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] BRCA1 regulates microRNA biogenesis via the DROSHA microprocessor complex2012

    • Author(s)
      Kawai S, Amano A
    • Journal Title

      Journal of Cell Biology

      Volume: 197(2) Pages: 201-208

    • DOI

      10.1083/jcb.201110008

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cardiovascular diseases and periodontal diseases2012

    • Author(s)
      Amano A
    • Journal Title

      Clinical Calcium

      Volume: 22 Pages: 43-48

    • Related Report
      2012 Annual Research Report
  • [Journal Article] Involvement of a periodontal pathogen, Porphyromonas gingivalis on the pathogenesis of nonalcoholic2012

    • Author(s)
      Yoneda M, Naka S, Nakano K, Wada K, Endo H, Mawatari H, Imajo K, Nomura R, Hokamura K, Ono M, Murata S, Tohnai I, Sumida Y, Shima T, Kuboniwa M, Umemura K, Kamisaki Y, Amano A, Okanoue T, Ooshima T, Nakajima A.
    • Journal Title

      BMC gastroenterology

      Volume: 12 Pages: 12-16

    • DOI

      10.1186/1471-230x-12-16

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development and evaluation of new primers for PCR-based identification of type II fimA of2012

    • Author(s)
      Moon JH, et al
    • Journal Title

      FEMS Immunology Medical Microbiology

      Volume: Nov 3(In press) Pages: 425-428

    • DOI

      10.1111/j.1574-695x.2011.00889.x

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Guidelines for the use and interpretation of assays for monitoring autophagy2012

    • Author(s)
      Klionsky DJ
    • Journal Title

      Autophagy

      Volume: 8 Pages: 445-544

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SNARE mediates autophagosome-lysosome fusion2012

    • Author(s)
      Furuta N
    • Journal Title

      Journal of Oral Bioscience

      Volume: 54 Pages: 83-85

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell entry and exit by periodontal pathogen Porphyromonas gingivalis2012

    • Author(s)
      Amano A
    • Journal Title

      Journal of Oral Bioscience

      Volume: 54 Pages: 54-57

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transition metal ions induce carnosinase activity in PepD-homologous protein from Porphyromonas gingivalis2012

    • Author(s)
      Aoki A, et al
    • Journal Title

      Microbial Pathogenesis

      Volume: 52 Pages: 17-24

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of a periodontal pathogen, Porphyromonas gingivalis on the pathogenesis of non-alcoholic fatty liver disease2012

    • Author(s)
      Yoneda M, et al
    • Journal Title

      BMC Gastroenterology

      Volume: 12 Pages: 16-16

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] BRCA1 regulates microRNA biogenesis via the DROSHA microprocessor complex2012

    • Author(s)
      Kawai S, et al
    • Journal Title

      Journal of Cell Biology

      Volume: 192 Pages: 201-208

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Insights into the pathogenesis of dental plaque : discoveries from proteomics2012

    • Author(s)
      Kuboniwa M, et al
    • Journal Title

      Expert Review

      Volume: (in press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 循環器疾患と歯周病2012

    • Author(s)
      天野敦雄, 他
    • Journal Title

      CLINICAL CALCIUM

      Volume: 22 Pages: 43-48

    • Related Report
      2011 Annual Research Report
  • [Journal Article] 病因論から再考する歯周治療2012

    • Author(s)
      天野敦雄
    • Journal Title

      障害者歯科

      Volume: 32 Pages: 1-7

    • NAID

      10030299367

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Characterization of aortic aneurysms in cardiovascular disease patients harboring Porphyromonas gingivalis2011

    • Author(s)
      Nakano K, et al
    • Journal Title

      Oral Diseases

      Volume: 17 Pages: 370-378

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cellular ATP synthesis mediated by type III sodium-dependent phosphate transporter Pit-1 is critical to chondrogenesis2011

    • Author(s)
      Sugita A, et al
    • Journal Title

      Journal of Biological Chemistry

      Volume: 286 Pages: 3094-3103

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exit of intracellular Porphyromonas gingivalis from gingival epithelial cells is mediated by endocytic recycling pathway2011

    • Author(s)
      Takeuchi H, et al
    • Journal Title

      Cellular Microbiology

      Volume: 13 Pages: 677-691

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The collagen-binding protein of Streptococcus mutans is involved in hemorrhagic stroke2011

    • Author(s)
      Nakano K, et al
    • Journal Title

      Nature Communications

      Volume: 2 Pages: 485-485

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Consideration on English education at Osaka University Graduate School of Dentistry2011

    • Author(s)
      Hamazaki Y, et al
    • Journal Title

      Journal of Osaka University Dental Society

      Volume: 56 Pages: 5-30

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Proliferation of smooth muscle cells stimulated with Porphyromonas gingivalis is inhibited by apple polyphenol2011

    • Author(s)
      Inaba H, et al
    • Journal Title

      Journal of Periodontology

      Volume: 82 Pages: 1616-1622

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell entry and exit by periodontal pathogen via recycling pathway2011

    • Author(s)
      Takeuchi H, et al
    • Journal Title

      Communicative & Integrative Biology

      Volume: 4 Pages: 587-589

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell entry and exit by periodontal pathogen Porphyromonas gingivalis2011

    • Author(s)
      Amano A, et al
    • Journal Title

      Journal of Oral Bioscience

      Volume: 54 Pages: 54-57

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 歯周病と4つの全身疾患2011

    • Author(s)
      天野敦雄, 他
    • Journal Title

      臨床薬理

      Volume: 42 Pages: 65-66

    • NAID

      10029432651

    • Related Report
      2011 Annual Research Report
  • [Presentation] Molecular basis of periodontal destruction by periodontal bacteria2013

    • Author(s)
      Amano A
    • Organizer
      2nd meeting of IADR-Asia Pacific Region
    • Place of Presentation
      Bangkok, Thailand
    • Year and Date
      2013-08-21
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 口腔から挑むBioResearch:Dental Scienceのときめき2013

    • Author(s)
      天野敦雄
    • Organizer
      第62回口腔衛生学会
    • Place of Presentation
      松本
    • Year and Date
      2013-05-16
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Strategy of periodontal bacteria for periodontal destruction2013

    • Author(s)
      Amano A
    • Organizer
      Seminar at School of Dentistry University of Louisville
    • Place of Presentation
      Louisville, Kentucky
    • Year and Date
      2013-03-18
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Strategy of periodontal bacteria for periodontal destruction2013

    • Author(s)
      Amano A
    • Organizer
      Seminar at Penn Dental
    • Place of Presentation
      Philadelphia, Pennsylvania
    • Year and Date
      2013-03-15
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] The autophagosome forms at ER#8722;mitochondria contact sites2012

    • Author(s)
      Hamasaki M
    • Organizer
      Annual meeting of American Society for Cell Biology
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2012-12-16
    • Related Report
      2012 Annual Research Report
  • [Presentation] Osaka university graduate school of dentistry opens the Frontier of Biodentistry2012

    • Author(s)
      Amano A
    • Organizer
      The first Japan-Thailand-Korea joint symposium on translational research in oral sciences
    • Place of Presentation
      Bangkok, Thailand
    • Year and Date
      2012-11-16
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Strategy of P. gingivalis for periodontal destruction2012

    • Author(s)
      Amano A
    • Organizer
      First international conference on Porphyromonas gingivalis and related bacterial species
    • Place of Presentation
      Nagasaki
    • Year and Date
      2012-08-28
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 基礎研究が指し示す歯周病因論2012

    • Author(s)
      天野敦雄
    • Organizer
      第61回口腔衛生学会
    • Place of Presentation
      横須賀
    • Year and Date
      2012-05-27
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Starategy of periodontal bacteria for periodontal destruction2012

    • Author(s)
      Amano A
    • Organizer
      The 2^<nd> International Joint Symposium on Oral and Dental Sciences
    • Place of Presentation
      Yogjakarta (Indonesia)(招待講演)
    • Year and Date
      2012-03-02
    • Related Report
      2011 Annual Research Report
  • [Presentation] 口腔領域の遺伝子診断「病因論から予測する歯周病発症リスク」2011

    • Author(s)
      天野敦雄
    • Organizer
      大阪府病院診療所歯科部長会・研修会
    • Place of Presentation
      ホテルモントレー大阪(大阪市)(招待講演)
    • Year and Date
      2011-12-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] 病因論から再考する歯周治療2011

    • Author(s)
      天野敦雄
    • Organizer
      障害者歯科学会教育講座、第28回日本障害者歯科学会学術大会
    • Place of Presentation
      福岡国際会議場(福岡市)(招待講演)
    • Year and Date
      2011-11-05
    • Related Report
      2011 Annual Research Report
  • [Presentation] Outer membrane vesicles function as offensive weapons of Porphyromonas gingrvalis2011

    • Author(s)
      Amano A
    • Organizer
      The Second Osaka Mahidol Chulalongkorn Joint Symposium
    • Place of Presentation
      Bangkok (Thailand)(招待講演)
    • Year and Date
      2011-10-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] Outer membrane vesicles function as offensive weapons of Porphyromonas gingivalis2011

    • Author(s)
      Amano A
    • Organizer
      13rd International Congress of Bacteriology and Applied Microbiology
    • Place of Presentation
      札幌コンベンションセンター(札幌市)(招待講演)
    • Year and Date
      2011-09-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] Strategy of periodontal bacteria for periodontal destruction2011

    • Author(s)
      Amano A
    • Organizer
      Periodontik Terkini, Universitas Gadjah Mada
    • Place of Presentation
      ガジャマダ大学(Indonesia)(招待講演)
    • Year and Date
      2011-07-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] 細菌感染症の転帰を決める細胞ロジスティクス機構の分子基盤解析2011

    • Author(s)
      天野敦雄, 他
    • Organizer
      新学術領域「細胞内ロジスティクス」班会議
    • Place of Presentation
      鳥羽シーサイドホテル(鳥羽市)
    • Year and Date
      2011-06-01
    • Related Report
      2011 Annual Research Report
  • [Book] オートファジー2012

    • Author(s)
      天野敦雄
    • Total Pages
      230
    • Publisher
      化学同人
    • Related Report
      2012 Annual Research Report
  • [Book] ビジュアル 歯周病を科学する2012

    • Author(s)
      天野敦雄
    • Total Pages
      348
    • Publisher
      クインテッセンス出版
    • Related Report
      2012 Annual Research Report
  • [Book] 歯周病を科学する2012

    • Author(s)
      天野敦雄, 他
    • Publisher
      クインテッセンス出版
    • Related Report
      2011 Annual Research Report
  • [Book] 病原菌の今日的意味2011

    • Author(s)
      天野敦雄, 他
    • Publisher
      医薬ジャーナル
    • Related Report
      2011 Annual Research Report

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Published: 2011-04-05   Modified: 2018-03-28  

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