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Blockade of renal malignant cycle by transcriptional regulation of SLCO transporter

Research Project

Project/Area Number 23390033
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical pharmacy
Research InstitutionTohoku University

Principal Investigator

ABE Takaaki  東北大学, 医工学研究科, 教授 (80292209)

Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2013: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2011: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Keywordsトランスポーター / 尿毒症物質 / GATA / AhR / 尿毒症 / インドキシル硫酸 / SLCO4C1 / 転写 / エリスロポエチン
Research Abstract

The accumulated uremic toxins inhibit the expression of various renal transporters and this inhibition may further reduce renal function and subsequently cause the accumulation of uremic toxins. Indoxyl sulfate, one of the potent uremic toxins, directly suppresses the renal-specific organic anion transporter SLCO4C1 expression through a transcription factor GATA3.
Administration of indoxyl sulfate in rats reduced renal expression of slco4c1 and under this condition, plasma level of guanidinosuccinate, one of the preferable substrates of slco4c1, was significantly increased without changing plasma creatinine. Furthermore, in 5/6 nephrectomized rats, treatment with oral adsorbent AST-120 significantly decreased plasma indoxyl sulfate level and conversely increased the expression of slco4c1. These data suggest that the removal of indoxyl sulfate and blocking its signal pathway may help to restore the SLCO4C1-mediated renal excretion of uremic toxins in CKD.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (46 results)

All 2014 2013 2012 2011 Other

All Journal Article (15 results) (of which Peer Reviewed: 10 results) Presentation (23 results) Remarks (3 results) Patent(Industrial Property Rights) (5 results) (of which Overseas: 2 results)

  • [Journal Article] Conformational Change in tRNA is an Early Indicator of Acute Cellular Damage with Prognostic Significance2014

    • Author(s)
      Mishima E., Inoue C., Saigusa D., Inoue R., Ito K., Ito S., Tomioka Y., Itoh K. and Abe T
    • Journal Title

      J . Am. Soc. Nephrol

      Volume: pii: ASN. 2013091001

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Conformational Change in tRNA is an Early Indicator of Acute Cellular Damage2014

    • Author(s)
      Mishima E.
    • Journal Title

      J. Am. Soc. Nephrol.

      Volume: 確定

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Indoxyl Sulfate Down-Regulates SLCO4C1 Transporter through Up-Regulation of GATA32013

    • Author(s)
      Akiyama Y, Kikuchi K, Saigusa D, Suzuki T, Takeuchi Y, Mishima E, Yamamoto Y, Ishida A, Sugawara D, Jinno D, Shima H, Toyohara T, Suzuki C, Souma T, Moriguchi T, Tomioka Y, Ito S, Abe T.
    • Journal Title

      PLoS One

      Volume: 8 Issue: 7 Pages: e66518-e66518

    • DOI

      10.1371/journal.pone.0066518

    • URL

      https://pure.teikyo.jp/en/publications/b41b65bc-bfe0-47fb-a7c3-8634d5a8a245

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mutation of the Mg^(2+) Transporter SLC41A1 Results in a Nephronophthisis-Like Phenotype.2013

    • Author(s)
      Hurd TW, Otto EA, Mishima E, Gee HY, Inoue H, Inazu M, Yamada H, Halbritter J, Seki G, Konishi M, Zhou W, Yamane T, Murakami S, Caridi G, Ghiggeri G, Abe T, Hildebrandt F
    • Journal Title

      J Am Soc Nephrol.

      Volume: 24 Issue: 6 Pages: 967-977

    • DOI

      10.1681/asn.2012101034

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A metabolomic approach to clarifying the effect of AST-120 on 5/6 nephrectomized rats by capillary electrophoresis with mass spectrometry (CE-MS).2012

    • Author(s)
      Akiyama Y.
    • Journal Title

      Toxins

      Volume: 4 Issue: 11 Pages: 1309-1322

    • DOI

      10.3390/toxins4111309

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] スタチンによる尿毒症物質排泄トランスポーター発現制御と腎不全治療2012

    • Author(s)
      鈴木健弘、阿部高明
    • Journal Title

      Therapeutic Research

      Volume: 33 Pages: 309-314

    • Related Report
      2011 Annual Research Report
  • [Journal Article] 尿毒素と腎線維化2012

    • Author(s)
      鈴木健弘、豊原敬文, 阿部高明, 他6名
    • Journal Title

      医学のあゆみ

      Volume: 240 Pages: 201-203

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Chronic Kidney Disease, Dyslipidemia, and Atherosclerosis2011

    • Author(s)
      Shoji T, Abe T, Matsuo H, Egusa G, Yamasaki Y, Kashihara N, Shirai K, Kashiwagi A
    • Journal Title

      J Atheroscler Thromb

      Volume: 184(Epub ahead of print)

    • NAID

      130004444596

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Metabolomic profiling of the autosomal dominant polycystic kidney diseaserat model2011

    • Author(s)
      Toyohara T, Suzuki T, Akiyama Y, Yoshihara D, Takeuchi Y, Mishima E, Kikuchi K, Suzuki C, Tanemoto M. Ito S, Nagao S, Soga T, Abe T
    • Journal Title

      Clin Exp Nephrol

      Volume: 15 Pages: 676-87

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transcriptional Regulation of Organic Anion Transporting Polypeptide SLCO4C1 as a New Therapeutic Modality to Prevent Chronic Kidney Disease2011

    • Author(s)
      Suzuki, T.
    • Journal Title

      J.Pharm.Sci.

      Volume: 100 Issue: 9 Pages: 3696-3707

    • DOI

      10.1002/jps.22641

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of transporter function and development to clinical application2011

    • Author(s)
      Toyohara T, Abe T
    • Journal Title

      Seikagaku

      Volume: 83 Pages: 323-8

    • NAID

      10029068254

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Screening of antibiotics that interact with organic anion-transporting polypeptides 1B1 and 1B3 using fluorescent probes2011

    • Author(s)
      Yamaguchi H, Takeuchi T, Okada M, Kobayashi M, Unno M, Abe T, Goto J, Hishinuma T, Shimada M, Mano N
    • Journal Title

      Biol Pharm Bull

      Volume: 34 Pages: 389-95

    • NAID

      130000657818

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Luminal alkalinization attenuates proteinuria-induced oxidative damage in proximal tubular cells2011

    • Author(s)
      Souma T, Abe M, Moriguchi T, Takai J, Yanagisawa-Miyazawa N, Shibata E, Akiyama Y, Toyohara T, Suzuki T, Tanemoto M, Abe T, Sato H, Yamamoto M, Ito S
    • Journal Title

      J Am Soc Nephrol

      Volume: 22 Pages: 635-48

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 甲状腺ホルモン輸送蛋白質2011

    • Author(s)
      鈴木健弘、阿部高明
    • Journal Title

      日本甲状腺学会雑誌

      Volume: 2 Pages: 174-177

    • Related Report
      2011 Annual Research Report
  • [Journal Article] 尿細管排泄機構と尿毒症物質:トランスポーター発現制御による腎不全治療2011

    • Author(s)
      鈴木健弘、阿部高明
    • Journal Title

      臨床薬理

      Volume: 42 Pages: 147-148

    • NAID

      10029432839

    • Related Report
      2011 Annual Research Report
  • [Presentation] CE-MS を用いた透析患者の病態に特有な尿毒症物質の同定2013

    • Author(s)
      秋山 泰利
    • Organizer
      第56回日本腎臓学会学術総会
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2013-05-12
    • Related Report
      2013 Final Research Report
  • [Presentation] エリスロポエチン産生を増強させる化合物群の探索と同定 (その1)2013

    • Author(s)
      佐原 利人
    • Organizer
      第56回日本腎臓学会学術総会
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2013-05-12
    • Related Report
      2013 Final Research Report
  • [Presentation] エリスロポエチン産生を増強させる化合物群の探索と同定 (その2)2013

    • Author(s)
      鈴木 雄介
    • Organizer
      第56回日本腎臓学会学術総会
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2013-05-12
    • Related Report
      2013 Final Research Report
  • [Presentation] tRNA の挙動検知はDNA ダメージよりも早期の虚血組織障害マーカーとなる2013

    • Author(s)
      三島 英換
    • Organizer
      第56回日本腎臓学会学術総会
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2013-05-10
    • Related Report
      2013 Final Research Report
  • [Presentation] 慢性腎臓病患者のスタチンによる腎保護効果の検討2012

    • Author(s)
      鈴木健弘、阿部高明
    • Organizer
      第24回腎と脂質研究会
    • Place of Presentation
      京都市
    • Year and Date
      2012-03-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] CKDにおけるトランスポーター発現低下メカニズムの解明~尿毒症物質蓄積の悪循環に対する新規治療~2012

    • Author(s)
      秋山泰利、阿部高明
    • Organizer
      第2回分子腎臓フォーラム
    • Place of Presentation
      京都市
    • Year and Date
      2012-01-21
    • Related Report
      2011 Annual Research Report
  • [Presentation] Renoprotective effects of statin in patients with chronic kidney disease2012

    • Author(s)
      Suzuki T, Saigusa D, Mishima E, Akiyama Y, Takeuchi Y, Sato H, Ito S, Abe T
    • Organizer
      Renal week 2012, ASN,
    • Place of Presentation
      San Diego, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Identifying the Uremic Compounds Specifically Involved in the Pathophysiology of Hemodialysis Patients by Capillary Electrophoresis-Mass Spectrometry2012

    • Author(s)
      Akiyama Y, Takeuchi Y, Mishima E, Suzuki T, Ito S, Soga T, Abe T
    • Organizer
      Renal week 2012, ASN
    • Place of Presentation
      San Diego, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] CKDにおけるトランスポーター発現低下メカニズムの解明~尿毒症物質蓄積の悪循環に対する新規治療~2011

    • Author(s)
      秋山泰利、阿部高明
    • Organizer
      第2回腎不全病態治療研究会
    • Place of Presentation
      東京都
    • Year and Date
      2011-12-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] Transcriptional regulation of uremic toxin transporter by uremic toxins2011

    • Author(s)
      鈴木健弘、阿部高明
    • Organizer
      第26回薬物動態学会年会
    • Place of Presentation
      広島市
    • Year and Date
      2011-11-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] Metabolomic Profiling of Uremic Solutes in CKD patients2011

    • Author(s)
      鈴木健弘、阿部高明
    • Organizer
      Renal week 2011, American Society of Nephrology
    • Place of Presentation
      Pennsylvania Convention Center, Philadelphia, Pennsylvania, USA
    • Year and Date
      2011-11-12
    • Related Report
      2011 Annual Research Report
  • [Presentation] Indoxyl Sulfate Causes Accumulation of Uremic Toxins through Down-Regulation of SLCO4C1 Transporter2011

    • Author(s)
      秋山泰利、阿部高明
    • Organizer
      Renal week 2011, American Society of Nephrology
    • Place of Presentation
      Pennsylvania Convention Center, Philadelphia, Pennsylvania, USA
    • Year and Date
      2011-11-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] Metabolomic Profiling of the Autosomal Dominant Polycystic Kidney Disease Rat Model2011

    • Author(s)
      豊原敬文、阿部高明
    • Organizer
      Renal week 2011, American Society of Nephrology
    • Place of Presentation
      Pennsylvania Convention Center, Philadelphia, Pennsylvania, USA
    • Year and Date
      2011-11-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] 尿毒症物質による尿毒症物質排泄トランスポーターSLCO4C1の転写制御と排泄促進の意義2011

    • Author(s)
      鈴木健弘、阿部高明
    • Organizer
      第34回日本高血圧学会総会
    • Place of Presentation
      宇都宮市
    • Year and Date
      2011-10-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] 腎尿細管の尿毒症物質排泄機構と腎不全治療2011

    • Author(s)
      鈴木健弘、阿部高明
    • Organizer
      第17回成人病の病因・病態の解明に関する研究会
    • Place of Presentation
      大阪市
    • Year and Date
      2011-07-02
    • Related Report
      2011 Annual Research Report
  • [Presentation] 尿毒症物質による尿毒症物質排泄トランスポーターSLCO4C1の転写制御の意義2011

    • Author(s)
      鈴木健弘、阿部高明
    • Organizer
      第54回日本腎臓学会学術総会
    • Place of Presentation
      横浜市
    • Year and Date
      2011-06-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] 尿毒症物質による尿毒症物質排泄トランスポーターSLCO4C1の転写制御の意義2011

    • Author(s)
      鈴木健弘、阿部高明
    • Organizer
      第6回トランスポーター研究会年会
    • Place of Presentation
      仙台市
    • Year and Date
      2011-06-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] Up-regulation of SLCO4C1 uremic toxin transporter expression and function by statins for therapeutics of chronic kidney disease2011

    • Author(s)
      鈴木健弘、阿部高明
    • Organizer
      7th International Society of Uremia Research and Toxicity (ISURT) 2011
    • Place of Presentation
      名古屋市
    • Year and Date
      2011-05-12
    • Related Report
      2011 Annual Research Report
  • [Presentation] スタチンによる尿毒症物質排泄トランスポーター発現制御と腎不全治療2011

    • Author(s)
      鈴木健弘、阿部高明
    • Organizer
      第84回日本内分泌学会学術総会
    • Place of Presentation
      神戸市
    • Year and Date
      2011-04-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] 三島 英換 tRNAの挙動検知はDNAダメージよりも早期の虚血組織障害マーカーとなる

    • Author(s)
      三島 英換
    • Organizer
      第56回日本腎臓学会学術総会
    • Place of Presentation
      東京国際フォーラム
    • Related Report
      2013 Annual Research Report
  • [Presentation] CE-MSを用いた透析患者の病態に特異的な尿毒症物質の同定

    • Author(s)
      秋山 泰利
    • Organizer
      第56回日本腎臓学会学術総会
    • Place of Presentation
      東京国際フォーラム
    • Related Report
      2013 Annual Research Report
  • [Presentation] エリスロポエチン産生を増強させる化合物群の探索と同定 (その1)

    • Author(s)
      佐原 利人
    • Organizer
      第56回日本腎臓学会学術総会
    • Place of Presentation
      東京国際フォーラム
    • Related Report
      2013 Annual Research Report
  • [Presentation] エリスロポエチン産生を増強させる化合物群の探索と同定 (その2)

    • Author(s)
      鈴木 雄介
    • Organizer
      第56回日本腎臓学会学術総会
    • Place of Presentation
      東京国際フォーラム
    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://plaza.umin.ac.jp/~takaabe/

    • Related Report
      2013 Final Research Report
  • [Remarks]

    • URL

      http://plaza.umin.ac.jp/~takaabe/

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.int2.med.tohoku.ac.jp/

    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] 腎機能障害の予防又は改善剤2013

    • Inventor(s)
      阿部 高明
    • Industrial Property Rights Holder
      阿部 高明
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-10-04
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] エリスロポエチン産生促進剤2013

    • Inventor(s)
      阿部 高明
    • Industrial Property Rights Holder
      阿部 高明
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-11-25
    • Related Report
      2013 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 腎機能障害の予防又は改善剤2013

    • Inventor(s)
      阿部高明
    • Industrial Property Rights Holder
      阿部高明
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-10-14
    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] エリスロポエチン産生促進剤2013

    • Inventor(s)
      阿部高明
    • Industrial Property Rights Holder
      阿部高明
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-11-25
    • Related Report
      2013 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] ヒトにおける新たな腎疾患マーカー物質2012

    • Inventor(s)
      阿部高明, 曽我朋義
    • Industrial Property Rights Holder
      東北大学, 慶應大学
    • Industrial Property Number
      2011-529823
    • Filing Date
      2012-02-14
    • Related Report
      2011 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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