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The role of MMP-10 in peritoneal fibrosis

Research Project

Project/Area Number 19K17706
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53040:Nephrology-related
Research InstitutionKyoto University

Principal Investigator

Toda Naohiro  京都大学, 医学研究科, 客員研究員 (30760615)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords中皮細胞 / 腹膜透析 / 炎症細胞 / 蛋白分解酵素 / MMP-10 / 腹膜線維化 / p38MAPK
Outline of Research at the Start

長期間の腹膜透析により、腹膜の線維化が認められる。腹膜線維症マウスの網羅的遺伝子解析から、タンパク分解酵素であるmatrix metalloproteinase-10 (MMP-10)に着目した。MMP-10ノックアウトマウスに腹膜線維症を惹起し、腹膜線維症に及ぼす影響を検討する。また、MMP-10誘導にp38MAPKが関与することから、p38MAPKもノックアウトマウスを用いて解析を行う。培養中皮細胞を用いてMMP-10の過剰発現や欠損状態が、線維化と血管新生に及ぼす影響について解析する。

Outline of Final Research Achievements

To elucidate the mechanism of peritoneal fibrosis caused by long-term peritoneal dialysis, we analyzed the role of matrix metalloproteinase-10 (MMP-10), which is upregulated in the peritoneum fibrosis. Intraperitoneal administration of chlorohexidine to MMP-10 knockout mice reduced peritoneal fibrosis compared to wild-type mice. TGF-β and Col1a1 were decreased in chlorohexidine MMP-10 knockout mice. Ccl2 and Emr1 expression, which are involved in inflammation, were also decreased. To investigate the effect of MMP-10 on peritoneal permeability, we performed a peritoneal equilibrium test and found no difference in peritoneal permeability and water removal between wild-type and MMP-10 knockout mice treated with chlorohexidine.
Furthermore, peritoneal mesothelial cells harvested from MMP-10 knockout mice as a primary culture system were examined with TNF-α stimulation. Expression of Ccl2 and TNF-α mRNA was decreased compared to wild-type mice, consistent with the in vivo results.

Academic Significance and Societal Importance of the Research Achievements

腹膜透析の合併症である腹膜線維化進行機序解明を行った研究であり、透過性亢進に関与しないものの腹膜線維化に関連する液性因子を同定した。社会的意義としては腹膜透析長期継続へのバイオマーカー、標的因子の候補の一つである。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (16 results)

All 2021 2020 2019 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (10 results) (of which Int'l Joint Research: 6 results,  Invited: 3 results) Remarks (1 results)

  • [Journal Article] Successful treatment of assisted automated peritoneal dialysis by using 4.25% glucose dialysate for elderly patients with refractory heart failure.2021

    • Author(s)
      17.Toda N, Iwaki R, Oishi K, Takasu Y, Komiya T.
    • Journal Title

      CEN Case Rep

      Volume: 10 Issue: 1 Pages: 121-125

    • DOI

      10.1007/s13730-020-00533-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Topical application of mupirocin to exit sites in patients on peritoneal dialysis: a systematic review and meta-analysis of randomized controlled trials.2020

    • Author(s)
      Yoko Obata, Miho Murashima, Naohiro Toda, Shuto Yamamoto, Yoshihiro Tsujimoto, Yasushi Tsujimoto, Hiraku Tsujimoto, Hidemichi Yuasa, Munekazu Ryuzaki, Yasuhiko Ito, Tadashi Tomo and Hidetomo Nakamoto
    • Journal Title

      Renal Replacement Therapy

      Volume: 6 Pages: 12-12

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Brachiocephalic Vein Occlusion from a Tunneled Hemodialysis Catheter2019

    • Author(s)
      Toda N, Asada S, Komiya T.
    • Journal Title

      Internal Medicine

      Volume: 58 Issue: 22 Pages: 3339-3340

    • DOI

      10.2169/internalmedicine.3354-19

    • NAID

      130007746080

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2019-11-15
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Connective tissue growth factor is correlated with peritoneal lymphangiogenesis2019

    • Author(s)
      Kinashi Hiroshi、Toda Naohiro、Sun Ting、Nguyen Tri Q.、Suzuki Yasuhiro、Katsuno Takayuki、Yokoi Hideki、Aten Jan、Mizuno Masashi、Maruyama Shoichi、Yanagita Motoko、Goldschmeding Roel、Ito Yasuhiko
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 12175-12175

    • DOI

      10.1038/s41598-019-48699-9

    • NAID

      120006958096

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Urgent-start peritoneal dialysis after laparoscopic dialysis catheter implantation: a single-center experience2019

    • Author(s)
      Naohiro Toda, Motoko Yanagita and Hideki Yokoi
    • Journal Title

      Renal Replacement Therapy

      Volume: 5 Pages: 43-43

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Matrix metalloproteinase-10欠損マウスにおける腹膜線維化の抑制効果の検討2020

    • Author(s)
      石村拓也,石井輝,大﨑啓介,戸田尚宏,森慶太,半田貴也,柳田素子,横井秀基
    • Organizer
      第63回日本腎臓学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Urgent-start peritoneal dialysis after laparoscopic dialysis catheter implantation.2019

    • Author(s)
      Toda N, Yanagita M, Yokoi H.
    • Organizer
      9th Asian pacific chapter meeting of the International Society for Peritoneal Dialysis
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Application of topical antibiotics ointment at the exit site of peritoneal dialysis patients.2019

    • Author(s)
      Toda N, Obata Y, Tagawa M, Yamamoto S, Tsujimoto Y,
    • Organizer
      9th Asian pacific chapter meeting of the International Society for Peritoneal Dialysis
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] PD苦手意識払拭講座2019

    • Author(s)
      戸田尚宏
    • Organizer
      第25回腹膜透析医学会学術集会・総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Matrix metalloproteinase-10 is a key molecule in aldosterone-induced glomerular injury in systemic guanylyl cyclase-A knockout mice2019

    • Author(s)
      Yokoi H,Osaki K, Kato Y, Toda N, Ishi A, Mori K P ,Kosaki K ,Kasahara M, Mukoyama M, Yanagita M.
    • Organizer
      WCN2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Role of matrix metalloproteinase-10 in peritoneal fibrosis2019

    • Author(s)
      Ishimura T, Ishii A, Osaki K, Toda N, Mori K P, Handa T , Yanagita M, Yokoi H
    • Organizer
      9th Asian pacific chapter meeting of the International Society for Peritoneal Dialysis
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Evaluation of mechanism on peritoneal fibrosis using genetically modified mice2019

    • Author(s)
      Yokoi H, Ishimura T, Toda N; Yanagita M
    • Organizer
      9th Asian pacific chapter meeting of the International Society for Peritoneal Dialysis
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Deletion of Matrix Metalloproteinase-10 Ameliorates Peritoneal Fibrosis2019

    • Author(s)
      Ishimura T, Ishi A, Osaki K, Toda N, Mori K P, Handa T, Yanagita M, Yokoi H
    • Organizer
      ASN2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 腹膜線維化・炎症に及ぼすCTGFとMMP-10の役割2019

    • Author(s)
      横井秀基,石村拓也,戸田尚宏,柳田素子
    • Organizer
      第25回日本腹膜透析医学会学術集会・総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Matrix metalloproteinase-10欠損による腹膜線維化の抑制効果2019

    • Author(s)
      石村拓也,石井輝,大崎啓介,戸田尚宏,森慶太,半田貴也,柳田素子,横井秀基
    • Organizer
      第25回日本腹膜透析医学会学術集会・総会
    • Related Report
      2019 Research-status Report
  • [Remarks] 京都大学大学院医学研究科 腎臓内科学

    • URL

      http://www.kidney-kyoto-u.jp/

    • Related Report
      2020 Annual Research Report

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Published: 2019-04-18   Modified: 2022-01-27  

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