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Establishment of new strategy targeting lymphangiogenesis in the patients with renal diseases

Research Project

Project/Area Number 15K09287
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Kidney internal medicine
Research InstitutionAichi Medical University (2017-2018)
Nagoya University (2015-2016)

Principal Investigator

Yasuhiko Ito  愛知医科大学, 医学部, 教授 (60402632)

Co-Investigator(Kenkyū-buntansha) 水野 正司  名古屋大学, 医学系研究科, 寄附講座教授 (20303638)
鈴木 康弘  名古屋大学, 医学系研究科, 寄附講座講師 (20584676)
坂田 史子  名古屋大学, 医学系研究科, 特任助教 (20726484)
武井 佳史  愛知学院大学, 薬学部, 教授 (70362233)
Project Period (FY) 2015-04-01 – 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 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords腹膜透析 / 腹膜機能不全 / リンパ管新生 / 血管新生 / 炎症 / 透過性亢進 / D/P Cr / リンパ管 / 食塩 / Lyve-1 / VEGFR-3 / VEGF-C / 腹膜透過性 / 腎間質障害
Outline of Final Research Achievements

Appropriate fluid balance is important for good outcomes in patients on peritoneal dialysis. The characteristic features of peritoneal injury with PD are fibrosis, inflammation and neoangiogenesis; however, these precise mechanisms remain unclear.
We investigated the 1) roles and pathophysiology of lymphangiogenesis in PD, 2) relationship between peritoneal fibrosis and angiogenesis, and 3) roles of high salt intake in PD. We conducted the studies using animal models, in vitro studies with mesothelial cells, fibroblasts, and macrophages, and human materials including peritoneal biopsy samples and PD effluent. In animal models Adeno-soluble VEGFR-3 effectively improve the drained volume by suppression of lymphangiogenesis, suggesting thatVEGFR-3 could be the new target to improve UF. Neoangiogenesis is associated with fibrosis by TGF-β1-VEGF-A pathway in mesothelial cells and fibroblasts. High salt intake induces the inflammation leading to the increase of peritoneal transport rates.

Academic Significance and Societal Importance of the Research Achievements

腹膜透析(PD)における除水不全の機序、対策が明らかになることによって、PD治療が長期に可能となり、PD患者負担が軽減する。ひいては医療経済にも好影響を与える。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (31 results)

All 2018 2017 2016 2015

All Journal Article (12 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 5 results,  Acknowledgement Compliant: 2 results) Presentation (19 results) (of which Int'l Joint Research: 12 results,  Invited: 2 results)

  • [Journal Article] Sodium chloride promotes tissue inflammation via osmotic stimuli in sub-total-nephrectomized mice.2017

    • Author(s)
      Sakata F., Ito Y., Mizuno M, Sawai A, Suzuki Y, Tomita T, Tawada M, Tanaka A, Hirayama A, Sagara A, Wada T, Maruyama S, Soga T, Matsuo S, Imai E, Takei Y.
    • Journal Title

      Lab Invest

      Volume: 97(4) Issue: 4 Pages: 432-446

    • DOI

      10.1038/labinvest.2017.4

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] High level of soluble C5b-9 complex in dialysis fluid is a predictor of poor prognosis in peritonitis in peritoneal dialysis patients.2017

    • Author(s)
      Matsuo S, Morgan BP, Ito Y.
    • Journal Title

      PLoS One

      Volume: in press

    • Related Report
      2016 Research-status Report
  • [Journal Article] Rat Models of Acute and/or Chronic Peritoneal Injuries Including Peritoneal Fibrosis and Peritoneal Dialysis Complications.2016

    • Author(s)
      Mizuno M, Ito Y.
    • Journal Title

      Methods Mol Biol

      Volume: 1397 Pages: 35-43

    • DOI

      10.1007/978-1-4939-3353-2_4

    • ISBN
      9781493933518, 9781493933532
    • Related Report
      2016 Research-status Report
  • [Journal Article] Recent analysis of status and outcomes of peritoneal dialysis2016

    • Author(s)
      Mizuno M., Ito Y, Skata F, Saka Y, Hiramatsu T, Tamai H, Mizutani M, Naruse T, Ohashi N, Kasuga H, Shimizu H, Kurata H, Kurata K, Suzuki S, Kido S, Tsuruta Y, Matsuoka T, Horie M, Naruyama S, Matsuo S.
    • Journal Title

      Clin Exp Nephrol

      Volume: in press Issue: 6 Pages: 961-971

    • DOI

      10.1007/s10157-016-1249-9

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Vascular endothelial cell injury is an important factor in the development of encapsulating peritoneal sclerosis in long-term peritoneal dialysis patients.2016

    • Author(s)
      Tawada M, Ito Y, Hamada C, Honda K, Mizuno M, Suzuki Y, Sakata F, Terabayashi T, Matsukawa Y, Maruyama S, Imai E, Matsuo S, Takei Y.
    • Journal Title

      PLoS One

      Volume: 11 Issue: 4 Pages: e0154644-e0154644

    • DOI

      10.1371/journal.pone.0154644

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Vascular endothelial growth factor receptor-3 is a novel target to improve net ultrafiltration in methylglyoxal-induced peritoneal injury2015

    • Author(s)
      Terabayashi T, Ito Y, Mizuno M, Suzuki Y, Kinashi H, Sakata F, Tomita T, Iguchi D, Tawada M, Nishio R, Maruyama S, Imai E, Matsuo S, Takei Y.
    • Journal Title

      Laboratory Investigation

      Volume: 95(9) Issue: 9 Pages: 1029-1043

    • DOI

      10.1038/labinvest.2015.87

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression of membrane complement regulators, CD46, CD55 and CD59, in mesothelial cells of patients on peritoneal dialysis therapy.2015

    • Author(s)
      Sei Y, Mizuno M, Suzuki Y, Imai M, Higashide K, Harris CL, Sakata F, Iguchi D, Fujiwara M, Kodera Y, Maruyama S, Matsuo S, Ito Y
    • Journal Title

      Molecular Immunology

      Volume: 153 Issue: 2 Pages: 302-309

    • DOI

      10.1016/j.molimm.2015.02.005

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Morphological caracteristics in peritoneum in patients with neutral peritoneal dialysis solution.2015

    • Author(s)
      Hamada C, Honda K, Kawanishi K, Nakamoto H, Ito Y, Sakurada T, Tanno Y, Mizumasa T, Miyazaki M, Moriishi M, Nakayama M
    • Journal Title

      Journal of Artifical Organs(in press 2015)

      Volume: Epub Issue: 3 Pages: 243-250

    • DOI

      10.1007/s10047-015-0822-4

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Successful Treatment of <i>Cryptococcus laurentii</i> Peritonitis in a Patient on Peritoneal Dialysis2015

    • Author(s)
      Asano M, Mizutani M, Nagahara Y, Inagaki K, Kariya T, Masamoto D, Urai M, Kaneko Y, Ohno H, Miyazaki Y, Mizuno M, Ito Y.
    • Journal Title

      Internal Medicine

      Volume: 54 Issue: 8 Pages: 941-944

    • DOI

      10.2169/internalmedicine.54.3586

    • NAID

      130005065248

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Calcified Amorphous Tumor in the Left Atrium in a Patient on Long-term Peritoneal Dialysis2015

    • Author(s)
      Tanaka A, Mizuno M, Suzuki Y, Oshima H, Sakata F, Ishikawa H, Tsukushi S, Ito Y
    • Journal Title

      Internal Medicine

      Volume: 54 Issue: 5 Pages: 481-485

    • DOI

      10.2169/internalmedicine.54.2967

    • NAID

      130004724006

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tubulointerstitial Fibrosis in Patients with IgG4 Related Kidney Disease: Pathological Findings on Repeat Renal Biopsy2015

    • Author(s)
      Haruna Arai, Hiroki Hayashi, Kazuo Takahashi, Shigehisa Koide, Waichi Sato, Midori Hasegawa, Yutaka Yamaguchi, Jan Aten, Yasuhiko Ito, Yukio Yuzawa
    • Journal Title

      Rheumatology International

      Volume: 印刷中 Issue: 6 Pages: 1093-1101

    • DOI

      10.1007/s00296-014-3153-5

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] The efficacy of tolvaptan as a diuretic for chronic kidney disease patients2015

    • Author(s)
      Tanaka A, Katsuno T, Ozaki T, Sakata F, Kato N, Suzuki Y, Kosugi T, Kato S, Tsuboi N, Sato W, Yasuda Y, Mizuno M, Ito Y, Matsuo S, Maruyama S.
    • Journal Title

      Acta Cariologica

      Volume: 70(2) Pages: 217-223

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] High Salt Intake Increases Baseline Peritoneal Transport Rate Through Local TonEBP Activation in Subtotal Nephrectomized Mice2018

    • Author(s)
      Sun T
    • Organizer
      米国腎臓学会(サンディエゴ)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] High Salt Intake Increases Baseline Peritoneal Transport Rate Through Local TonEBP Activation in Subtotal Nephrectomized Mice2018

    • Author(s)
      Sun T
    • Organizer
      国際腹膜透析学会(バンクーバー)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Neutral peritoneal dialysis solutions reduce morphological damages in the patients with long-term peritoneal membrane treatment2017

    • Author(s)
      Ito Y., Tawada M, Hamada C, Mizuno M, Suzuki Y, Sakata F, Maruyama S
    • Organizer
      the 8th Asia Pacific Chapter Meeting of International Society for PeritonealDialysis
    • Place of Presentation
      Guangzhou, China,
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] VEGF-D plays a subtle role in the development of lymphangiogenesis in methylglyoxal-induced peritoneal injury2017

    • Author(s)
      T Sun, Y Ito, M Mizuno, Y Suzuki, F Sakata, T Terabayashi, T Tomita, S Maruyama
    • Organizer
      the 8th Asia Pacific Chapter Meeting of International Society for PeritonealDialysis
    • Place of Presentation
      Guangzhou, China,
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] Pathophysiology of peritoneal dysfunction in PD2017

    • Author(s)
      Yasuhiko Ito
    • Organizer
      the 8th Asia Pacific Chapter Meeting of International Society for PeritonealDialysis
    • Place of Presentation
      Guangzhou, China,
    • Year and Date
      2017-03-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pathophysiology of peritoneal dysfunction in PD2017

    • Author(s)
      Yasuhiko Ito
    • Organizer
      International Society of Peritoneal Dialysis Asian-Pacific Chapter
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Neutral peritoneal dialysis solutions prevent morphological changes in the patients with long-term peritoneal membrane treatment2017

    • Author(s)
      Yasuhiko Ito
    • Organizer
      International Society of Peritoneal Dialysis Asian-Pacific Chapter
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] VEGF-D plays a subtle role in the development of lymphangiogenesis in methylglyoxal-induced peritoneal injury2017

    • Author(s)
      Ting Sun, Yasuhiko Ito
    • Organizer
      International Society of Peritoneal Dialysis Asian-Pacific Chapter
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] TGF-β-VEGF-A pathway induces neoangiogenesis in peritoneal fibrosis of peritoneal dialysis.2016

    • Author(s)
      T Kariya, Y Ito, M Mizuno, Y Suzuki, F Sakata, T Terabayashi, T Ishii, M Tawada, D Iguchi, S Maruyama, S Matsuo.
    • Organizer
      53RD ERA-EDTA CONGRESS
    • Place of Presentation
      Vienna, Austria
    • Year and Date
      2016-05-23
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Sodium Chloride Promotes Tissue Inflammation via Osmotic Stimuli in Subtotal Nephrectomized Mice.2015

    • Author(s)
      Fumiko Sakata, Yasuhiko Ito, Masashi Mizuno, Yasuhiro Suzuki, Takeshi Terabayashi, Takako Tomita, Mitsuhiro Tawada, Shoichi Maruyama, Enyu Imai, Yoshifumi Takei, Seiichi Matsuo
    • Organizer
      ASN Kidney Week 2015
    • Place of Presentation
      San Diego(USA)
    • Year and Date
      2015-11-03
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Vascular Endothelial Cell Damage Is an Important Factor in the Development of Encapsulating Peritoneal Sclerosis.2015

    • Author(s)
      Mitsuhiro Tawada, Yasuhiko Ito, Chieko Hamada, Kazuho Honda, Masashi Mizuno, Yasuhiro Suzuki, Fumiko Sakata, Shoichi Maruyama, Yoshifumi Takei, Seiichi Matsuo
    • Organizer
      ASN Kidney Week 2015
    • Place of Presentation
      San Diego(USA)
    • Year and Date
      2015-11-03
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pathophysiology of the peritoneal membrane damage: fibrosis, angiogenesis and lymphangiogenesis2015

    • Author(s)
      Yasuhiko Ito
    • Organizer
      The 7th Asia Pacific Chapter Meeting of International Society for Peritoneal Dialysis
    • Place of Presentation
      大邱(Korea)
    • Year and Date
      2015-09-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of encapsular peritoneal sclerosis(EPS)-like peritonitis in rat and complement activation2015

    • Author(s)
      Daiki iguchi, Masashi Mizuno, Emi Shigemoto, Fumiko Sakata, Yasuhiro Suzuki, Alan Okada, Hidechika Okada, Shoichi Maruyama, Seiichi Matsuo, Yasuhiko Ito
    • Organizer
      The 15th European Meeting on Complement in Human Disease
    • Place of Presentation
      Uppsala(Sweden)
    • Year and Date
      2015-06-27
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 腎不全マウスにおいて食塩負荷は、浸透圧刺激によってMCP-1、sgk-1を誘導し炎症を惹起する2015

    • Author(s)
      坂田 史子、伊藤 恭彦、狩谷 哲芳、多和田 光弘、富田 貴子、寺林 武、鈴木 康弘、水野 正司、松尾 清一
    • Organizer
      第58回日本腎臓学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-06-06
    • Related Report
      2015 Research-status Report
  • [Presentation] ANCA関連血管炎における喫煙と再燃との関係について2015

    • Author(s)
      山口 真、安藤 昌彦、加藤 佐和子、小杉 智規、佐藤 和一、坪井 直毅、安田 宜成、水野 正司、伊藤 恭彦、松尾 清一、丸山 彰一
    • Organizer
      第58回日本腎臓学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-06-06
    • Related Report
      2015 Research-status Report
  • [Presentation] 排液中TGF-β1蛋白濃度は腹膜組織線維化、腹膜機能低下を反映する2015

    • Author(s)
      鈴木 康弘、寺林 武、坂田 史子、坪井 直毅、水野 正司、丸山 彰一、伊藤 恭彦、松尾 清一
    • Organizer
      第58回日本腎臓学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-06-06
    • Related Report
      2015 Research-status Report
  • [Presentation] 血管内皮細胞障害がEPS発症の最大のリスクファクターである2015

    • Author(s)
      多和田 光弘、伊藤 恭彦、寺林 武、坂田 史子、鈴木 康弘、水野 正司、濱田 千江子、本田 一穂、丸山 彰一、松尾 清一
    • Organizer
      第58回日本腎臓学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-06-05
    • Related Report
      2015 Research-status Report
  • [Presentation] 腹膜透析患者の腹膜中皮細胞における膜補体制御因子の発現2015

    • Author(s)
      水野 正司、清 祐美、井口 大旗、東出 慶子、坂田 史子、鈴木 康弘、今井 優樹、松尾 清一、伊藤 恭彦
    • Organizer
      第58回日本腎臓学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-06-05
    • Related Report
      2015 Research-status Report
  • [Presentation] メタボローム解析を用いた腹膜透過性の検討2015

    • Author(s)
      富田 貴子、伊藤 恭彦、坂田 史子、鈴木 康弘、水野 正司、丸山 彰一、平山 明由、松尾 清一
    • Organizer
      第58回日本腎臓学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-06-05
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2020-03-30  

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