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Molecular mechanism of inflammation-related miRNA in tissue repair and antisense oligodeoxynucleotide development

Research Project

Project/Area Number 24689069
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypePartial Multi-year Fund
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionNagasaki University

Principal Investigator

MORI Ryoichi  長崎大学, 医歯薬学総合研究科(医学系), 講師 (30509310)

Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥24,830,000 (Direct Cost: ¥19,100,000、Indirect Cost: ¥5,730,000)
Fiscal Year 2015: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2013: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
Fiscal Year 2012: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywords皮膚創傷治癒 / miRNA / Foxo / 炎症 / 創傷治癒 / 感染 / 皮膚創傷治癒過程 / ケロイド / FoxOファミリー / アンチセンスオリゴ / microRNA
Outline of Final Research Achievements

I investigated function of miR-223 and Foxo1 in skin wound healing. Skin wound healing in miR-223 KO mice was delayed concomitant with altered neutrophil activation. I showed that miR-223 KO mice undergo prolonged acute inflammatory responses at wound sites due to miR-223 KO-derived neutrophils exhibiting increased hyperoxidative bursts. Intriguingly, S. aureus-infected miR-223 KO mice showed markedly faster skin wound healing than S. aureus-infected wild-type mice. Our data indicate that the molecular targeting of miR-223 may regulate the healing of bacterium-infected chronic skin wounds.
Foxo1 heterozygous mice led to accelerated skin wound healing with enhanced keratinocyte migration and reduced scarring accompanied by an attenuated inflammatory response. Transient knockdown of Foxo1 at the wound site by local delivery of antisense oligo enhanced skin wound healing. Overall, molecular targeting of FOXO1 may improve the quality of healing and reduce pathological scarring.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (31 results)

All 2015 2014 2013 2012 Other

All Int'l Joint Research (1 results) Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (22 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Book (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] ブリストル大学/ロンドン大学キングスカレッジ(英国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Potency of umbilical cord blood- and Wharton’s jelly-derived mesenchymal stem cells for scarless wound healing2015

    • Author(s)
      Doi H., Kitajima Y., Luo L., Yan C., Tateishi S., Ono Y., Urata Y., Goto S., Mori R., Masuzaki H., Shimokawa I., Hirano A. & Li T. S.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 18844-18844

    • DOI

      10.1038/srep18844

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ephrin-Bs drive junctional downregulation and actin stress fiber disassembly to enable wound re-epithelialisation2015

    • Author(s)
      Nunan R., Campbell J., Mori R., Pitulescu M. E., Jiang W. G., Harding K. G. , Adams H. G., Nobes C. D. & Martin P.
    • Journal Title

      Cell Rep

      Volume: 13 Issue: 7 Pages: 1380-1380

    • DOI

      10.1016/j.celrep.2015.09.085

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Upregulation of cytochrome c oxidase subunit 6b1 (Cox6b1) and formation of mitochondrial supercomplexes: implication of Cox6b1 in the effect of calorie restriction.2015

    • Author(s)
      Kim S. E., Mori R., Komatsu T., Chiba T., Hayashi H., Park S., Sugawa M. D., Dencher N. A. & Shimokawa I.
    • Journal Title

      Age (Dordr)

      Volume: 37 Issue: 3 Pages: 9787-9787

    • DOI

      10.1007/s11357-015-9787-8

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Overexpression of the adiponectin gene mimics the metabolic and stress resistance effects of calorie restriction, but not the anti-tumor effect2015

    • Author(s)
      Kamohara R, Yamaza H, Tsuchiya T, Komatsu T, Park S, Hayashi H, Chiba T, Mori R, Otabe S, Yamada K, Nagayasu T, Shimokawa I
    • Journal Title

      Experimental Gerontology

      Volume: 64 Pages: 46-54

    • DOI

      10.1016/j.exger.2015.02.011

    • NAID

      120006987178

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The life-extending effect of dietary restriction requires Foxo3 in mice2015

    • Author(s)
      Shimokawa I, Komatsu T, Hayashi N, Kim SE, Kawata T, Park S, Hayashi H, Yamaza H, Chiba T, Mori R
    • Journal Title

      Aging Cell

      Volume: - Issue: 4 Pages: 707-707

    • DOI

      10.1111/acel.12340

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reduced FOXO1 accelerates skin wound healing and attenuates scarring.2014

    • Author(s)
      Mori R, Tanaka K, de Kerckhove M, Okamoto M, Kashiyama K, Tanaka K, Kim SE, Kawata T, Komatsu T, Park S, Ikematsu K, Hirano A, Martin P, Shimokawa I
    • Journal Title

      American Journal of Pathology

      Volume: 184 Issue: 9 Pages: 2465-2479

    • DOI

      10.1016/j.ajpath.2014.05.012

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 皮膚創傷治癒過程における miR-223 の機能解析2015

    • Author(s)
      森 亮一
    • Organizer
      第45回 日本創傷治癒学会
    • Place of Presentation
      JPタワーホール&カンファレンス(東京都千代田区)
    • Year and Date
      2015-11-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] miR-223 regulates neutrophil activation in the acute inflammatory response during skin wound healing2015

    • Author(s)
      森 亮一
    • Organizer
      Gordon Research Conference (Tissue Repair & Regeneration)
    • Place of Presentation
      New London (USA)
    • Year and Date
      2015-06-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 組織修復及び炎症制御に関与する microRNA の病態生理学的解析2015

    • Author(s)
      森 亮一
    • Organizer
      第104回日本病理学会総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-04-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] Identification of inflammation-related miRNAs in skin wound healing2014

    • Author(s)
      森 亮一
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 皮膚創傷治癒改善効果のある核酸医薬の開発2014

    • Author(s)
      森 亮一
    • Organizer
      東京理科大学 トランスレーショナルリサーチセンター キックオフミーティング
    • Place of Presentation
      東京理科大学 野田キャンパス(千葉県野田市)
    • Year and Date
      2014-09-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Reduced FOXO1 accelerates skin wound healing and attenuates scarring2014

    • Author(s)
      Mori R
    • Organizer
      EMBO Conferences, The molecular and cellular basis of regeneration and tissue repair
    • Place of Presentation
      Sant Feliu de Guixols, Spain
    • Year and Date
      2014-09-06 – 2014-09-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] Pathophysiological role of inflammation-related microRNA in murine skin wound healing2014

    • Author(s)
      Mori R
    • Organizer
      FEBS-EMBO Meeting
    • Place of Presentation
      Paris, France
    • Year and Date
      2014-08-30 – 2014-09-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] 転写因子FoxO1の発現抑制は皮膚創傷治癒を促進し瘢痕形成を減弱する2014

    • Author(s)
      森 亮一
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島国際会議場(広島県広島市)
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] 炎症制御を主体とした皮膚創傷治癒に効果のある核酸医薬の作成2013

    • Author(s)
      森 亮一
    • Organizer
      BIOtech 2013 in Japan
    • Place of Presentation
      東京ビッグサイト (東京都江東区)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 皮膚創傷治癒改善効果のあるオリゴヌクレオチドの同定及び機能解析2013

    • Author(s)
      森 亮一
    • Organizer
      第36回日本基礎老化学会
    • Place of Presentation
      大阪大学中之島センター (大阪府大阪市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 皮膚創傷治癒改善効果のあるオリゴヌクレオチドの同定及び機能解析2013

    • Author(s)
      森 亮一
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      ロイトン札幌、札幌芸文館 (北海道札幌市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] The roles of transcription factor FoxO family members, and of post-transcriptional regulation by inflammation-related microRNAs, in skin wound healing2013

    • Author(s)
      Mori R
    • Organizer
      Gordon Research Conferences, Tissue repair & regeneration
    • Place of Presentation
      アメリカ
    • Related Report
      2013 Annual Research Report
  • [Presentation] 皮膚創傷治癒過程における炎症反応特異的 microRNA の同定及び機能解析2013

    • Author(s)
      森 亮一
    • Organizer
      第5回日本RNAi研究会
    • Place of Presentation
      グランドプリンスホテル広島 (広島県広島市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] FoxO1制御に基づく皮膚創傷治癒医薬2013

    • Author(s)
      森 亮一
    • Organizer
      BIOJapan 2013
    • Place of Presentation
      パシフィコ横浜 (神奈川県横浜市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 老化関連遺伝子及び組織修復の分子相関:寿命制御転写因子 FoxO1 は皮膚創傷治癒及び線維化を制御する2013

    • Author(s)
      森 亮一
    • Organizer
      第43回日本創傷治癒学会
    • Place of Presentation
      別府湾ロイヤルホテル (大分県速見郡)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 皮膚創傷治癒過程における転写因子 FoxO ファミリーの機能解析2013

    • Author(s)
      森 亮一
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド (兵庫県神戸市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 皮膚創傷治癒過程における炎症反応特異的microRNAの同定及び機能解析2012

    • Author(s)
      森 亮一
    • Organizer
      第101回日本病理学会総会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Identification of Argonute2-circulating microRNA complexes in blood plasmaof calorie-restricted and high fat diet-induced obese mice2012

    • Author(s)
      Ryoichi Mori
    • Organizer
      International Symposium of Asian Association ofAging Research 2012 in Fukuoka - Biology of Aging andDisorders-
    • Place of Presentation
      Tsukushi Kaikan (Fukuoka)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Identification of Argonute2-circulating microRNA complexes in blood plasmaof calorie-restricted and high fat diet-induced obese mice2012

    • Author(s)
      森 亮一
    • Organizer
      第4回日本RNAi研究会
    • Place of Presentation
      グランドプリンスホテル広島(広島県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Identification of Argonute2-circulating microRNA complexes in blood plasmaol calorie-restricted and high fat diet-induced obese mice2012

    • Author(s)
      Ryoichi Mori
    • Organizer
      The 4th EMBO meeting
    • Place of Presentation
      Nice Acropolis (France)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 皮膚創傷治癒過程における炎症反応特異的microRNAの同定及び機能解析2012

    • Author(s)
      森 亮一
    • Organizer
      第42回日本創傷治癒学会
    • Place of Presentation
      かでる2. 7 (北海道)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 次世代シーケンサーを用いたカロリー制限及び肥満マウス血漿中に存在するmicroRNAの網羅的同定2012

    • Author(s)
      森 亮一
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡(福岡県)
    • Related Report
      2012 Annual Research Report
  • [Book] Role of the forkhead box O family and neuropeptide Y in calorie restriction. Aging Mechanisms: Longevity, Metabolism, and Brain Aging2015

    • Author(s)
      Mori R, Park S. & Shimokawa I
    • Total Pages
      430
    • Publisher
      Springer
    • Related Report
      2015 Annual Research Report
  • [Patent(Industrial Property Rights)] 創傷または線維症の治療剤2014

    • Inventor(s)
      森 亮一、下川 功
    • Industrial Property Rights Holder
      森 亮一、下川 功
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-03-26
    • Related Report
      2013 Annual Research Report
    • Overseas

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Published: 2012-04-24   Modified: 2022-01-31  

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