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The effects of food protein-derived metabolite, indoxyl sulfate, on progression of renal disease.

Research Project

Project/Area Number 23700830
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Applied health science
Research InstitutionHokkaido University (2012)
Nagoya University (2011)

Principal Investigator

SHIMIZU Hidehisa  北海道大学, 大学院・農学研究院, 特任講師 (10547532)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords慢性腎不全 / 尿毒症物質 / トリプトファン代謝物 / インドキシル硫酸 / 細胞老化 / 線維化 / 炎症反応 / 繊維化
Research Abstract

In patients with chronic kidney disease (CKD), serum indoxyl sulfate is elevated. Therefore, the present study examined what molecules are activated and expressed by indoxyl sulfate, and how indoxyl sulfate promotes CKD. Indoxyl sulfate activated ERK, p38, JNK, NF-?B, p53, Stat3, and CREB in proximal tubular cells. In addition, the expression of NOX4, TGF-?1, Smad3, ?-SMA, MCP-1, ICAM-1, and angiotensinogen was upregulated. Current study demonstrated that indoxyl sulfate induced macrophage infiltration, cellular senescence, and fibrosis through activation and expression of above-mentioned factors in process of CKD progression.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (34 results)

All 2013 2012 2011 Other

All Journal Article (21 results) (of which Peer Reviewed: 21 results) Presentation (10 results) (of which Invited: 1 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Organochlorine pesticides and heavy metals in fish from Lake Awassa; Ethiopia: Insights from stable isotope analysis.2013

    • Author(s)
      Yared BY, Ikenaka Y, Nakayama SMM, Saengtienchai A, Watanabe K, Ishizuka M
    • Journal Title

      Chemosphere

      Volume: 91 Pages: 857-863

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Accumulation and biological effects of metals in wild rats in mining areas of Zambia2013

    • Author(s)
      Nakayama SMM, Ikenaka Y, Hamada K, Muzandu K, Choongo K, Yabe J, Umemura T, Ishizuka M.
    • Journal Title

      Environmental Monitoring and Assessment

      Volume: 185 Pages: 4907-4918

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Metal distribution in tissues of free-range chickens near a lead-zinc mine in Kabwe, Zambia.2013

    • Author(s)
      Yabe J, Nakayama SMM, Ikenaka Y, Muzandu K, Choongo K, Mainda G, Kabeta N, Ishizuka M, Umemura T.
    • Journal Title

      Environ Toxicol Chem

      Volume: 32(1) Pages: 189-92

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] GIS-based source estimation of Cu pollution in Lake Itezhi-tezhi and metal accumulation profiles in Oreochromis spp. from both field and laboratory studies2013

    • Author(s)
      Shouta M.M. Nakayama, Yoshinori Ikenaka, Kaampwe Muzandu, Kennedy Choongo, John Yabe, Taro Muroya, Shigeho Ijiri, Masao Minagawa, Takashi Umemura, Mayumi Ishizuka.
    • Journal Title

      Arch Environ Contam Toxicol

      Volume: 64(1) Pages: 119-29

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Indoxyl sulfate, a uremic toxin, downregulates renal expression of Nrf2 through activation of NF-κB.2013

    • Author(s)
      Bolati D, Shimizu H, Yisireyili M, Nishijima F, Niwa T.
    • Journal Title

      BMC Nephrol.

      Volume: 14 Issue: 1 Pages: 56-56

    • DOI

      10.1186/1471-2369-14-56

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CREB, NF-κB, and NADPH oxidase coordinately upregulate indoxyl sulfate-induced angiotensinogen expression in proximal tubular cells.2013

    • Author(s)
      Shimizu H, Saito S, Higashiyama Y, Nishijima F, Niwa T.
    • Journal Title

      Am J Physiol Cell Physiol.

      Volume: 304 Issue: 7 Pages: C685-C692

    • DOI

      10.1152/ajpcell.00236.2012

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Indoxyl sulfate enhances p53-TGF-β1-Smad3 pathway in proximal tubular cells.2013

    • Author(s)
      Shimizu H, Yisireyili M, Nishijima F, Niwa T.
    • Journal Title

      Am J Nephrol.

      Volume: 37 Issue: 2 Pages: 97-103

    • DOI

      10.1159/000346420

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Indoxyl sulfate upregulates renal expression of ICAM-1 via production of ROS and activation of NF-κB and p53 in proximal tubular cells.2013

    • Author(s)
      Shimizu H, Yisireyili M, Higashiyama Y, Nishijima F, Niwa T.
    • Journal Title

      Life Sci.

      Volume: 92 Issue: 2 Pages: 143-148

    • DOI

      10.1016/j.lfs.2012.11.012

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytochrome P450 3A mRNA expression along goat and rat gastrointestinal tracts.2012

    • Author(s)
      Dominic MUREITHI, Wageh Sobhy DARWISH, Yoshinori IKENAKA, Laetitia KANJA, Mayumi ISHIZUKA.
    • Journal Title

      Jpn. J. Vet. Res

      Volume: 60(4) Pages: 205-10

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Accumulation of metals in the liver and kidneys of cattle from agricultural areas in Lusaka, Zambia2012

    • Author(s)
      Yabe J, Nakayama SMM, Ikenaka Y, Muzandu K, Ishizuka M, Umemura T.
    • Journal Title

      J Vet Med Sci

      Volume: 74(10) Pages: 1345-7

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The nucleotide sequence of metallothioneins (MT) in liver of the Kafue lechwe (Kobus leche kafuensis) and their potential as biomarkers of heavy metal pollution of the Kafue River.2012

    • Author(s)
      M'kandawire E, Syakalima M, Muzandu K, Pandey G, Simuunza M, Nakayama SM, Kawai YK, Ikenaka Y, Ishizuka M.
    • Journal Title

      Gene.

      Volume: 506(2) Pages: 310-6

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of environmental lead contamination on cattle in a lead/zinc mining area: changes in cattle immune systems on exposure to lead in vivo and in vitro.2012

    • Author(s)
      Ikenaka Y, Nakayama SMM, Muroya T, Yabe J, Konnai S, Darwish WS, Muzandu K, Choongo K, Mainda G, Teraoka H, Umemura T, Ishizuka M.
    • Journal Title

      Environ Toxicol Chem

      Volume: 31(10) Pages: 2300-5

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Transcriptional profiling of inflammatory cytokine genes in African buffaloes (Syncerus caffer) infected with Theileria parva.2012

    • Author(s)
      Okagawa T, Konnai S, Mekata H, Githaka N, Suzuki S, Kariuki E, Gakuya F, Kanduma E, Shirai T, Ikebuchi R, Ikenaka Y, Ishizuka M, Murata S, Ohashi K.
    • Journal Title

      Vet Immunol Immunopathol

      Volume: 148(3-4) Pages: 373-9

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Metal and metalloid levels and bio-accumulation characteristics in soil, sediment, land plants and hippopotami (Hippopotamus amphibius L) from the South Luangwa National Park, Zambia.2012

    • Author(s)
      Nakayama SM, Ikenaka Y, Muzandu K, Choongo K, M'kandawire E, Yasuda J,Ishizuka M.
    • Journal Title

      Ecotoxicol Environ Saf

      Volume: 80 Pages: 333-8

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular cloning and characterization of Th1 and Th2 cytokines of African buffalo (Syncerus caffer).2012

    • Author(s)
      Suzuki S, Konnai S, Okagawa T, Githaka NW, Kariuki E, Gakuya F, Kanduma E, Shirai T, Ikebuchi R, Ikenaka Y, Ishizuka M, Murata S, Ohashi K.
    • Journal Title

      Int J Immunogenet

      Pages: 170-82

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Stat3 contributes to indoxyl sulfate-induced inflammatory and fibrotic gene expression and cellular senescence.2012

    • Author(s)
      Shimizu H, Yisireyili M, Nishijima F, Niwa T.
    • Journal Title

      Am J Nephrol.

      Volume: 36 Issue: 2 Pages: 184-189

    • DOI

      10.1159/000341515

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Indoxyl sulfate upregulates renal expression of MCP-1 via production of ROS and activation of NF-κB, p53, ERK, and JNK in proximal tubular cells.2012

    • Author(s)
      Shimizu H, Bolati D, Higashiyama Y, Nishijima F, Shimizu K, Niwa T.
    • Journal Title

      Life Sciences

      Volume: 90 Pages: 525-530

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] 野生動物の化学物質感受性と生体防御機構2011

    • Author(s)
      池中良徳、石塚真由美
    • Journal Title

      安全工学

      Volume: 50(2) Pages: 80-80

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Phase-II conjugation ability for PAH metabolism in amphibians: Characteristics and inter-species differences.2011

    • Author(s)
      Ueda H, Ikenaka Y, Nakayama SM, Tanaka-Ueno T, Ishizuka M.
    • Journal Title

      Aquat Toxicol

      Volume: 105(3-4) Pages: 337-343

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Metal and metalloid contamination in roadside soil and wild rats around a Pb-Zn mine in Kabwe, Zambia.2011

    • Author(s)
      Nakayama SMM, Ikenaka Y, Hamada K, Muzandu K, Choongo K, Teraoka H, Mizuno N, Ishizuka M.
    • Journal Title

      Environmental Pollution

      Volume: 159 Pages: 175-18

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Occurrence, distribution and ecological risk assessment of DDTs and heavy metals in surface sediments from Lake Awassa ?Ethiopian Rift Valley Lake.

    • Author(s)
      Yohannes YB, Ikenaka Y, Saengtienchai A, Watanabe KP, Nakamyama SMM, Ishizuka M.
    • Journal Title

      Environ Sci Pollut Res

      Volume: (in press)

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Presentation] Effect of mining activity on wild and domestic animals: Case study of lead ? zink mining area, Kabwe, Zambia2013

    • Author(s)
      Yoshinori Ikenaka
    • Organizer
      日本学術会議北海道地区会議主催学術講演会
    • Place of Presentation
      北海道大学学術交流会館小講堂
    • Year and Date
      2013-03-01
    • Related Report
      2012 Final Research Report
  • [Presentation] 両生類の異物代謝機構の特徴と種差2012

    • Author(s)
      池中良徳
    • Organizer
      第21回環境化学討論会
    • Place of Presentation
      愛媛県県民文化会館(ひめぎんホール)
    • Related Report
      2012 Final Research Report
  • [Presentation] 鳥類における薬物代謝の特徴:ピレンをモデル化合物として2012

    • Author(s)
      池中良徳
    • Organizer
      第21回環境化学討論会
    • Place of Presentation
      愛媛県県民文化会館(ひめぎんホール)
    • Related Report
      2012 Final Research Report
  • [Presentation] 薬物代謝第II相抱合反応の種差:多環芳香族炭化水素の抱合反応と哺乳動物で観察された種差2012

    • Author(s)
      池中良徳
    • Organizer
      第21回環境化学討論会
    • Place of Presentation
      愛媛県県民文化会館(ひめぎんホール)
    • Related Report
      2012 Final Research Report
  • [Presentation] 腎血管系の老化に対する尿毒症物質インドキシル硫酸の影響2012

    • Author(s)
      清水英寿
    • Organizer
      創薬薬理フォーラム 第20回シンポジウム
    • Place of Presentation
      東京 ( 日本薬学会 長井記念館)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Stat3 is involved in indoxyl sulfate-induced inflammatory and fibrotic gene expression and cellular senescence in proximal tubular cells.2012

    • Author(s)
      Niwa, T., Nishijima, F., Shimizu, H.
    • Organizer
      American Society of Nephrology
    • Place of Presentation
      San Diego, USA (San Diego Convention Center)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Indoxyl sulfate, a uremic toxin, downregulates renal expression of Nrf2 through activation of NF-κB.2012

    • Author(s)
      Niwa, T., Bolati, D., Yisireyili, M., Nishijima, F., Shimizu, H.
    • Organizer
      American Society of Nephrology
    • Place of Presentation
      San Diego, USA (San Diego Convention Center)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Indoxyl sulfate upregulates renal expression of ICAM-1 via production of ROS and activation of NF-κB and p53 in proximal tubular cells.2012

    • Author(s)
      Shimizu, H., Niwa. T.
    • Organizer
      16th International Congress on Nutrition and Metabolism in Renal Disease
    • Place of Presentation
      Honolulu, USA (Hilton Hawaiian Village)
    • Related Report
      2012 Annual Research Report
  • [Presentation] インドキシル硫酸によるMCP‐1の発現メカニズムの解析2012

    • Author(s)
      清水英寿, デリナル ポラテ, ムテリフ グリヌル, アデリベキ イリシャテ, イスリ メメット, 下山泰彦, 東山幸弘, 西島冬彦, 丹羽利充
    • Organizer
      第55回 日本腎臓学会
    • Place of Presentation
      横浜 ( パシフィコ横浜)
    • Related Report
      2012 Annual Research Report
  • [Presentation] インドキシル硫酸によるTGF‐β1の発現制御機構及びTGF‐β1とのクロストークの検討2012

    • Author(s)
      清水英寿, デリナル ポラテ, ムテリフ グリヌル, アデリベキ イリシャテ, イスリ メメット, 下山泰彦, 東山幸弘, 西島冬彦, 丹羽利充
    • Organizer
      第55回 日本腎臓学会
    • Place of Presentation
      横浜( パシフィコ横浜)
    • Related Report
      2012 Annual Research Report
  • [Book] 獣医学・応用動物科学系学生のための野生動物学2013

    • Author(s)
      村田浩一 坪田敏男
    • Publisher
      野生動物と環境汚染
    • Related Report
      2012 Final Research Report
  • [Remarks] 北海道大学アフリカ研究会

    • URL

      http://aa.vetmed.hokudai.ac.jp/africa/

    • Related Report
      2012 Final Research Report
  • [Remarks] 北海道大学大学院獣医学研究科毒性学教室

    • URL

      http://tox.vetmed.hokudai.ac.jp/

    • Related Report
      2012 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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