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Development of novel theraputic agents targeting (pro) renin receptor

Research Project

Project/Area Number 16K11279
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionHokkaido University

Principal Investigator

Kanda Atsuhiro  北海道大学, 医学研究院, 特任講師 (80342707)

Co-Investigator(Kenkyū-buntansha) 喜多 俊介  北海道大学, 薬学研究院, 特任助教 (10702003)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords(プロ)レニン受容体 / 受容体結合プロレニン系 / 炎症 / 血管新生 / レニン・アンジオテンシン系 / (プロ)レニン受容体 / 網脈絡膜疾患 / 慢性炎症
Outline of Final Research Achievements

(Pro)renin receptor is known to regulate activations of tissue RAS and RAPS, and involved in the pathogenesis of several ocular disorders. However, its physiological functions remain unclear. The goal of this study is to develop a novel agent which can inhibit (P)RR functions, and determine its safety and efficacy in vitro and in vivo.

Academic Significance and Societal Importance of the Research Achievements

現在、眼科領域の分子標的療法では抗VEGF療法が臨床応用されたが、VEGFは進行期病態のメインプレーヤーでありRAPS活性化の下流で動く分子である。この臨床病期には他の炎症関連分子も動いているため、抗VEGF療法のみで病態を制御することには限界がある。(プロ)レニン受容体(つまりRAPSの活性化抑制)を創薬ターゲットとした本研究成果は、多くの病態分子を抑制できる上流での介入戦略として、より効率の良い治療の実現につながることが期待されている。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report

Research Products

(47 results)

All 2019 2018 2017 2016

All Journal Article (22 results) (of which Peer Reviewed: 16 results,  Open Access: 11 results,  Acknowledgement Compliant: 3 results) Presentation (22 results) (of which Int'l Joint Research: 6 results,  Invited: 9 results) Book (2 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] TGF-β-SNAIL axis induces Muller glial-mesenchymal transition in the pathogenesis of idiopathic epiretinal membrane2019

    • Author(s)
      Kanda A, Noda K, Hirose I, Ishida S
    • Journal Title

      Scientific Reports

      Volume: 9 Pages: 673-673

    • DOI

      10.1038/s41598-018-36917-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Galectin-1 promotes choroidal neovascularization and subretinal fibrosis mediated via epithelial-mesenchymal transition2019

    • Author(s)
      Wu Di、Kanda Atsuhiro、Liu Ye、Kase Satoru、Noda Kousuke、Ishida Susumu
    • Journal Title

      FASEB J

      Volume: 33 Pages: 2498-2513

    • DOI

      10.1096/fj.201801227r

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased plasma galectin-1 correlates with advanced glycation end products and interleukin-1 β in patients with proliferative diabetic retinopathy2019

    • Author(s)
      Hase K, Kanda A, Noda K, Ishida S
    • Journal Title

      International Journal of Ophthalmology

      Volume: 12 Pages: 692-694

    • DOI

      10.18240/ijo.2019.04.28

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical Features of Japanese Patients With Anti-α-enolase Antibody?Positive Autoimmune Retinopathy: Novel Subtype of Multiple Drusen2018

    • Author(s)
      Ando Ryo、Saito Wataru、Kanda Atsuhiro、Kase Satoru、Fujinami Kaoru、Sugahara Michitaka、Nakamura Yosuke、Eguchi Shuichiro、Mori Shohei、Noda Kousuke、Shinoda Kei、Ishida Susumu
    • Journal Title

      American Journal of Ophthalmology

      Volume: 196 Pages: 181-196

    • DOI

      10.1016/j.ajo.2018.08.044

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Proteolytic cleavage of vascular adhesion protein-1 induced by vascular endothelial growth factor in retinal capillary endothelial cells2018

    • Author(s)
      Yoshida Shiho、Murata Miyuki、Noda Kousuke、Matsuda Takashi、Saito Michiyuki、Saito Wataru、Kanda Atsuhiro、Ishida Susumu
    • Journal Title

      Japanese Journal of Ophthalmology

      Volume: 62 Issue: 2 Pages: 256-264

    • DOI

      10.1007/s10384-017-0555-4

    • ISSN
      0021-5155, 1613-2246
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pathologic roles of receptor-associated prorenin system in idiopathic epiretinal membrane.2017

    • Author(s)
      Dong Y,Kanda A, Noda K, Saito W, Ishida S
    • Journal Title

      Sci Rep

      Volume: 7 Pages: 44266-44266

    • DOI

      10.1038/srep44266

    • NAID

      120006219867

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Systemic factors related to soluble (pro)renin receptor in plasma of patients with proliferative diabetic retinopathy2017

    • Author(s)
      Hase Keitaro、Kanda Atsuhiro、Hirose Ikuyo、Noda Kousuke、Ishida Susumu
    • Journal Title

      PLoS ONE

      Volume: 12

    • DOI

      10.1371/journal.pone.0189696

    • NAID

      120006406688

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Novel Single-Strand RNAi Therapeutic Agent Targeting the (Pro)renin Receptor Suppresses Ocular Inflammation2017

    • Author(s)
      Kanda Atsuhiro、Ishizuka Erdal Tan、Shibata Atsushi、Matsumoto Takahiro、Toyofuku Hidekazu、Noda Kousuke、Namba Kenichi、Ishida Susumu
    • Journal Title

      Mol Ther Nucleic Acids

      Volume: 7 Pages: 116-126

    • DOI

      10.1016/j.omtn.2017.01.001

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 慢性炎症と糖尿病網膜症2017

    • Author(s)
      神田敦宏、石田 晋
    • Journal Title

      糖尿病診療マスター

      Volume: 15 Pages: 851-855

    • Related Report
      2017 Research-status Report
  • [Journal Article] 糖尿病網膜症の病態研究と進歩2017

    • Author(s)
      神田敦宏、石田 晋
    • Journal Title

      Diabetes Frontier

      Volume: 28 Pages: 273-276

    • Related Report
      2017 Research-status Report
  • [Journal Article] 糖尿病網膜症における受容体結合プロレニン系の関与2017

    • Author(s)
      神田敦宏
    • Journal Title

      日本糖尿病眼学会誌

      Volume: 21 Pages: 63-65

    • Related Report
      2017 Research-status Report
  • [Journal Article] 炎症性網脈絡膜疾患に対する新規治療薬開発に成功~日本独自の RNA 干渉法を用いた分子標的核酸医薬~. 北海道大学プレスリリースより2017

    • Author(s)
      神田敦宏、石田 晋
    • Journal Title

      北海道大学大学院医学研究科/医学部医学科広報

      Volume: 71 Pages: 19-19

    • Related Report
      2017 Research-status Report
  • [Journal Article] A novel single-strand RNAi therapeutic agent targeting (pro)renin receptor suppresses ocular inflammation2017

    • Author(s)
      Kanda A, Ishizuka ET, Shibata A, Matsumoto T, Toyofuku H, Noda K, Namba K, Ishida S
    • Journal Title

      Mol Ther Nucleic Acids

      Volume: in press

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Receptor-associated prorenin system contributes to development of inflammation and angiogenesis in proliferative diabetic retinopathy2017

    • Author(s)
      Kanda A, Ishida S.
    • Journal Title

      Inflamm Regen

      Volume: in press

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Evaluation of the safety and tolerability of conjunctival ring for posterior segment of the eye2017

    • Author(s)
      Kinoshita S, Ohguchi T, Noda K, Murata M, Yasueda S, Obata H, Matsunaga T, Fukushima T, Kanda A, Ishida S
    • Journal Title

      Curr Eye Res

      Volume: in press

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Improvements of visual function and outer retinal morphology following spontaneous regression of cancer in anti-recoverin cancer-associated retinopathy2017

    • Author(s)
      Suimon Y, Saito W, Hirooka K, Kanda A, Kitai H, Sakakibara-Konishi J, Ishida S
    • Journal Title

      Am J Ophthalmol Case Rep. in press 5.Dong Y,

      Volume: in press

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Phosphorylation of alphaB-crystallin in epiretinal membrane of human proliferative diabetic retinopathy.2016

    • Author(s)
      Dong Y, Dong Z, Kase S, Ando R, Fukuhara J, Kinoshita S, Inafuku S, Tagawa Y, Ishizuka ET, Saito W, Murata M, Kanda A, Noda K, Ishida S
    • Journal Title

      Int J Ophthalmol.

      Volume: 9 Pages: 1100-1105

    • DOI

      10.18240/ijo.2016.08.03

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of vascular endothelial growth factor-C by tumor necrosis factor-α in the conjunctiva and pterygium2016

    • Author(s)
      Dong Y, Kase S, Dong Z, Fukuhara J, Tagawa Y, Ishizuka ET, Murata M, Shinmei Y, Ohguchi T, Kanda A, Noda K, Ishida S
    • Journal Title

      Int J Mol Med

      Volume: 38 Pages: 545-550

    • DOI

      10.3892/ijmm.2016.2647

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of geranylgeranylacetone on the protection of retinal ganglion cells in a mouse model of normal tension glaucoma.2016

    • Author(s)
      Dong Z, Shinmei Y, Dong Y, Inafuku S, Fukuhara J, Ando R, Kitaichi N, Kanda A, Tanaka K, Noda K, Harada T, Chin S, Ishida S.
    • Journal Title

      Heliyon.

      Volume: 2

    • DOI

      10.1016/j.heliyon.2016.e00191

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vitreous levels of vascular endothelial growth factor-B in proliferative diabetic retinopathy2016

    • Author(s)
      Kinoshita S, Noda K, Saito W, Kanda A, Ishida S
    • Journal Title

      Acta Ophthalmol

      Volume: -

    • DOI

      10.1111/aos.12969

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 糖尿病網膜症における受容体結合プロレニン系の関与(総説)2016

    • Author(s)
      神田敦宏
    • Journal Title

      第30回日本糖尿病合併症学会・第21回日本糖尿病眼学会総会合同シンポジウム.糖尿病合併症

      Volume: 30 Pages: 26-28

    • Related Report
      2016 Research-status Report
  • [Journal Article] エイジングからみた糖尿病網膜症2016

    • Author(s)
      神田敦宏、石田 晋
    • Journal Title

      眼科

      Volume: 58 Pages: 643-649

    • Related Report
      2016 Research-status Report
  • [Presentation] Increased plasma galectin-1 is correlated with advanced glycation end products and interleukin-1β in patients with proliferative diabetic retiopathy2018

    • Author(s)
      Hase K, Kanda A, Noda K, Ishida S.
    • Organizer
      Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting: Honolulu, Hawaii
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Therapeutic effect of novel single-stranded RNAi agent targeting (Pro) renin receptor in ocular inflammation2018

    • Author(s)
      Kanda A, Liu Y, Ishizuka ET, Noda K, Ishida S.
    • Organizer
      33rd Asia-Pacific Academy of Ophthalmology Congress (APAO): Hong Kong, China;
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 受容体結合プロレニン系に対する核酸医薬による眼炎症病態の抑制2018

    • Author(s)
      神田敦宏、石田 晋.
    • Organizer
      第38回日本眼薬理学会、長崎
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脈絡膜血管新生と線維化におけるガレクチン-1の関与2018

    • Author(s)
      神田敦宏、Wu Di、野田航介、石田 晋.
    • Organizer
      第22回眼創傷治癒研究会、奈良
    • Related Report
      2018 Annual Research Report
  • [Presentation] 増殖糖尿病網膜症患者における血漿ガレクチン-1と炎症関連分子との相関解析2018

    • Author(s)
      長谷敬太郎、神田敦宏、野田航介、石田 晋.
    • Organizer
      第122回日本眼科学会総会、大阪
    • Related Report
      2018 Annual Research Report
  • [Presentation] Systemic factors related to soluble (pro)renin receptor in plasma of patients with proliferative diabetic retinopathy2018

    • Author(s)
      長谷敬太郎、神田敦宏、石田 晋.
    • Organizer
      第10回(プロ)レニン受容体フォーラム、東京
    • Related Report
      2018 Annual Research Report
  • [Presentation] 新規血管新生因子ガレクチン-1のアフリベルセプトによる阻害と糖尿病網膜症における病態形成への関与.2018

    • Author(s)
      神田敦宏.
    • Organizer
      Gunma Macular Academy、群馬
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 糖尿病における眼内炎症性メデイエーター ―受容体結合プロレニン系―. シンポジウム「なぜ糖尿病で失明するのか ~内科の意見、眼科の意見」.2018

    • Author(s)
      神田敦宏.
    • Organizer
      第18回日本抗加齢医学会総会、大阪
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Therapeutic effect of novel single-stranded RNAi agent targeting (pro)renin receptor in ocular inflammation2018

    • Author(s)
      Kanda A, Liu Y, Ishizuka ET, Noda K, Ishida S
    • Organizer
      Asia-Pacific Academy of Ophthalmology (APAO)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] (プロ)レニン受容体特異的一本鎖RNA干渉による眼炎症病態の抑制2017

    • Author(s)
      神田敦宏、石塚タンエルダル、劉 野、野田航介、石田 晋
    • Organizer
      第17回日本抗加齢医学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 糖尿病網膜症における(プロ)レニン受容体の病態形成への関与解明と阻害薬開発. YIA受賞講演.2017

    • Author(s)
      神田敦宏
    • Organizer
      第32回日本糖尿合併症学会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] (プロ)レニン受容体特異的一本鎖RNA干渉による眼炎症病態の抑制. 優秀演題受賞講演(基礎系)2017

    • Author(s)
      神田敦宏
    • Organizer
      第17回日本抗加齢医学会総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 受容体結合プロレニン系を標的とした網脈絡膜疾患治療. 教育セミナー「網膜疾患に対する基礎研究の進め方―思考の過程とその成果―」2017

    • Author(s)
      神田敦宏
    • Organizer
      第121回日本眼科学会総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 受容体結合プロレニン系を介した眼疾患病態形成機序の解明と創薬開発. ランチョンセミナー「バイエル レチナ・アワード」2017

    • Author(s)
      神田敦宏
    • Organizer
      第121回日本眼科学会総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 眼炎症性疾患の病態形成における受容体結合プロレニン系の関与2017

    • Author(s)
      神田敦宏
    • Organizer
      全身性炎症疾患の病因・病態の解明に関する研究助成 第6回研究発表会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] アフリベルセプト新規結合タンパク質ガレクチン-1による糖尿病網膜症における病態形成への関与2016

    • Author(s)
      神田敦宏、董陽子、野田航介、齋藤航、石田 晋
    • Organizer
      第39回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] flibercept traps galectin-1, an angiogenic factor associated with diabetic  retinopathy2016

    • Author(s)
      Kanda A
    • Organizer
      2016 Autumn Meeting of Ophthalmological Society of Taiwan (TOS)
    • Place of Presentation
      Chung Gung Memorial Hospital(Taiwan)
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Galectin-1 is associated with progression of diabetic retinopathy2016

    • Author(s)
      Kanda A, Dong Y, Noda K, Saito W, Ishida S
    • Organizer
      XXⅡ Biennial Meeting of the International Society for Eye Research(ISER)
    • Place of Presentation
      京王プラザホテル(東京都・新宿区)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Galectin-1 is an angiogenic factor associated with proliferative diabetic retinopathy : Novel target for aflibeccept2016

    • Author(s)
      Kanda A, Noda K, Saito W, Ishida S
    • Organizer
      Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting
    • Place of Presentation
      Washington State Convention Center(USA)
    • Year and Date
      2016-05-01
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 血管新生因子ガレクチン-1のアフリベルセプトによる阻害と糖尿病網膜症における関与2016

    • Author(s)
      神田敦宏、野田航介、齋藤 航、石田 晋
    • Organizer
      第120回日本眼科学会総会
    • Place of Presentation
      仙台国際センター・東北大学百周年記念会館(宮城県・仙台市)
    • Year and Date
      2016-04-07
    • Related Report
      2016 Research-status Report
  • [Presentation] アフリベルセプト新規結合タンパク質ガレクチン-1による糖尿病網膜症における病態形成への関与2016

    • Author(s)
      神田敦宏、董 陽子、野田航介、齋藤 航、石田 晋.
    • Organizer
      第6回わかもと先進眼科医療研究会(Wakamoto conference of Advanced Medicine of Ophthalmology in Tokyo; WACAMOTO)
    • Place of Presentation
      ロイヤルパークホテル(東京都・中央区)
    • Related Report
      2016 Research-status Report
  • [Presentation] タンパク質間相互利用作用解析を用いた眼疾患・基礎研究. スキルトランスファー「眼科基礎研究スキルトランスファー ~基本戦術とスキルを身につけよう~」2016

    • Author(s)
      神田敦宏
    • Organizer
      第120回日本眼科学会総会
    • Place of Presentation
      仙台国際センター・東北大学百周年記念会館(宮城県・仙台市)
    • Related Report
      2016 Research-status Report
    • Invited
  • [Book] 糖尿病合併症学会誌 322018

    • Author(s)
      神田敦宏
    • Publisher
      糖尿病合併症学会
    • Related Report
      2018 Annual Research Report
  • [Book] 大規模臨床試験(全身投与) まとめてズバッと解説! 知っているようで知らない新しい糖尿病網膜症診療2016

    • Author(s)
      神田敦宏
    • Total Pages
      268
    • Publisher
      メジカルビュー社
    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] プロレニン遺伝子またはプロレニン受容体遺伝子の発現を抑制する一本鎖核酸分子およびその用途2016

    • Inventor(s)
      石田 晋、神田敦宏他
    • Industrial Property Rights Holder
      北海道大学、東京医大、(株)ボナック
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016
    • Acquisition Date
      2017
    • Related Report
      2017 Research-status Report
    • Overseas

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Published: 2016-04-21   Modified: 2020-03-30  

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