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Molecular mechanism of transportsome in chronic kidney disease and the involvement of thyroid hormone

Research Project

Project/Area Number 25460652
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied pharmacology
Research InstitutionKumamoto University

Principal Investigator

Ayaka Suenaga  熊本大学, 薬学部, 講師 (20040313)

Co-Investigator(Kenkyū-buntansha) MARUYAMA Toru  熊本大学, 薬学部, 教授 (90423657)
OTAGIRI Masaki  崇城大学, 薬学部, 教授 (80120145)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords腎障害 / 二次性副甲状腺機能亢進症 / 副甲状腺ホルモン / トランスポーター / 尿毒症物質 / 甲状腺ホルモン / 腎疾患 / 慢性腎障害
Outline of Final Research Achievements

Hyperuricemia occurs with increasing frequency among patients with hyperparathyroidism. However, the molecular mechanism by which serum parathyroid hormone (PTH) regulates serum urate levels remains unknown. Here we show that, in rats with secondary hyperparathyroidism (SHPT), serum urate levels are increased and urate excretion in the intestine and kidney is decreased, presumably due to the downreguration of the intestinal and renal membrane expression of a urate exporter ABCG2. These effects were prevented by the administration of the calcimimetic PTH suppressor, cinacalcet. In Caco-2 cells, the plasma membrane expression of ABCG2 was downregulated by PTH. Clinical studies showed that treatment with cinacalcet resulted in significant reductions in serum urate levels in SHPT patients. These results suggest that PTH downregulates ABCG2 expression, and thereby suppresses intestinal and renal urate excretion, and that the effects of PTH can be prevented by a cinacalcet treatment.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (20 results)

All 2016 2015 2014 2013 Other

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 3 results,  Acknowledgement Compliant: 3 results) Presentation (15 results) (of which Invited: 5 results) Remarks (1 results)

  • [Journal Article] Continuous Reduction of Protein-Bound Uraemic Toxins with Improved Oxidative Stress by Using the Oral Charcoal Adsorbent AST-120 in Haemodialysis Patients.2015

    • Author(s)
      Yamamoto S, Kazama JJ, Omori K, Matsuo K, Takahashi Y, Kawamura K, Matsuto T, Watanabe H, Maruyama T, Narita I.
    • Journal Title

      Sci Rep.

      Volume: N/A Issue: 1 Pages: 14381-14381

    • DOI

      10.1038/srep14381

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] p-Cresyl sulfate, a uremic toxin, causes vascular endothelial and smooth muscle cell damages by inducing oxidative stress.2015

    • Author(s)
      Watanabe H, Miyamoto Y, Enoki Y, Ishima Y, Kadowaki D, Kotani S, Nakajima M, Tanaka M, Matsushita K, Mori Y, Kakuta T, Fukagawa M, Otagiri M, Maruyama T
    • Journal Title

      Pharmacol Res Perspect

      Volume: 3 Issue: 1

    • DOI

      10.1002/prp2.92

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Human organic anion transporters function as a high-capacity transporter for p-cresyl sulfate, a uremic toxin2014

    • Author(s)
      Watanabe H, Sakaguchi Y, Sugimoto R, Kaneko K, Iwata H, Kotani S, Nakajima M, Ishima Y, Otagiri M, Maruyama T
    • Journal Title

      Clin Exp Nephrol

      Volume: 18 Issue: 5 Pages: 814-20

    • DOI

      10.1007/s10157-013-0902-9

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] S-nitrosated α-1-acid glycoprotein kills drug-resistant bacteria and aids survival in sepsis2013

    • Author(s)
      Watanabe K, Ishima Y, Akaike T, Sawa T, Kuroda T, Ogawa W, Watanabe H, Suenaga A, Kai T, Otagiri M, Maruyama T
    • Journal Title

      FASEB J

      Volume: 27 Pages: 391-398

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 慢性腎臓病における腎-多臓器連関に関わる尿毒素の関与とその分子機構2016

    • Author(s)
      渡邊 博志、異島 優、小田切 優樹、丸山 徹
    • Organizer
      日本薬学会 第136年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 副甲状腺ホルモンよるABCG2 の発現抑制は二次性副甲状腺機能亢進症における尿酸値の上昇に関与する2015

    • Author(s)
      杉本 龍星、渡邊 博志、榎木 裕紀、異島 優、田中 元子、松下 和孝、駒場大峰、深川 雅史、小田切 優樹、丸山 徹
    • Organizer
      第6回 腎不全研究会
    • Place of Presentation
      東京:全社協・灘尾ホール
    • Year and Date
      2015-12-12
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Suppression of ABCG2 expression by parathyroid hormone enhances urate accumulation in secondary hyperparathyroidism2015

    • Author(s)
      Ryusei Sugimoto, Hiroshi Watanabe, Yuki Enoki, Yu Ishima, Motoko Tanaka, Kazutaka Matsushita, Masafumi Fukagawa, Masaki Otagiri, Toru Maruyama
    • Organizer
      Asian Federation for Pharmaceutical Sciences 2015
    • Place of Presentation
      Thailand , Rama Gardens Hotel
    • Year and Date
      2015-11-25
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 副甲状腺ホルモンは ABCG2 の発現抑制を介して血清尿酸値を上昇させる2015

    • Author(s)
      杉本 龍星、渡邊 博志、榎木 裕紀、異島 優、田中 元子、松下 和孝、 駒場 大峰、深川 雅史、小田切 優樹、丸山 徹
    • Organizer
      第37回 生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      熊本大学薬学部
    • Year and Date
      2015-11-19
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] シナカルセトは副甲状腺ホルモンが介在するABCG2発現抑制を解除することで尿酸排泄を促進する2015

    • Author(s)
      杉本 龍星、渡邊 博志、榎木 裕紀、異島 優、田中 元子、松下 和孝、深川 雅史、小田切 優樹、丸山 徹
    • Organizer
      第30回日本薬物動態学会
    • Place of Presentation
      東京:タワーホール船堀
    • Year and Date
      2015-11-12
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 丸山 徹、異島 優、成底 徹、小谷 俊介、中島 誠、渡邊 博志、小田切 優樹2015

    • Author(s)
      尿毒症物質インドキシル硫酸の酸化修飾体に関する構造特性と生物活性
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] OAT-dependent cellular accumulation of p-cresyl sulfate, a uremic toxin, causes vascular endothelial and smooth muscle cell damages by inducing oxidative stress2014

    • Author(s)
      Hiroshi Watanabe, Yohei Miyamoto, Yuki Enoki, Yu Ishima, Masafumi Fukagawa, Masaki Otagiri and Toru Maruyama
    • Organizer
      19th North American ISSX Meeting and 29th JSSX Meeting
    • Place of Presentation
      Hilton San Francisco, California, USA
    • Year and Date
      2014-10-20 – 2014-10-23
    • Related Report
      2014 Research-status Report
  • [Presentation] 尿毒症物質パラクレジル硫酸によるNADPH oxidase活性化を介した尿細管及び血管障害作用2014

    • Author(s)
      渡邊 博志、宮本 洋平、異島 優、深川 雅史、小田切 優樹、丸山 徹
    • Organizer
      第26回腎とフリーラジカル研究会
    • Place of Presentation
      産業労働センター ウインクあいち
    • Year and Date
      2014-09-20
    • Related Report
      2014 Research-status Report
  • [Presentation] 尿毒症物質 p‐クレジル硫酸の酸化ストレス誘導を介した血管障害作用2014

    • Author(s)
      渡邊 博志、宮本 洋平、榎木 裕紀、異島 優、深川 雅史、小田切 優樹、丸山 徹
    • Organizer
      第57回日本腎臓学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-07-04 – 2014-07-06
    • Related Report
      2014 Research-status Report
  • [Presentation] エリスロポエチン骨髄デリバリーシステムの腎性貧血治療への応用2014

    • Author(s)
      丸山徹、田口和明、宮崎裕理、渡邊博志、宗慶太郎、末永綾香、異島優、小田切優樹
    • Organizer
      日本薬学会第134年会2014/3/27-30(熊本)
    • Place of Presentation
      熊本大学
    • Related Report
      2013 Research-status Report
  • [Presentation] 遺伝子組換え型糖鎖付加アルブミンによるクッパー細胞選択的チオール送達は急性肝障害を改善する2013

    • Author(s)
      前田仁志(D2)、平田憲史郎、渡邊博志、異島 優、末永綾香、小田切優樹、丸山 徹
    • Organizer
      第35回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      東京大学
    • Related Report
      2013 Research-status Report
  • [Presentation] 一酸化窒素付加型アルブミンによる抗癌剤耐性克服効果とその機序解明2013

    • Author(s)
      異島 優、原 茉梨絵、甲斐俊哉、渡邊博志、末永綾香、小田切優樹、丸山 徹
    • Organizer
      第35回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      東京大学
    • Related Report
      2013 Research-status Report
  • [Presentation] クッパー細胞選択的チオール送達によるアセトアミノフェン肝障害治療法の開発2013

    • Author(s)
      前田 仁志(D2)、平田 憲史郎 、渡邊 博志、異島 優、末永 綾香、小田切 優樹、丸山 徹
    • Organizer
      日本薬剤学会第28年会
    • Place of Presentation
      ウインクあいち
    • Related Report
      2013 Research-status Report
  • [Presentation] S-nitrosated α-1-acid glycoprotein kills drug-resistant bacteria and aids survival in sepsis2013

    • Author(s)
      Kaori Watanabe (D3), Yu Ishima, Teruo Kuroda, Wakano Ogawa, Hiroshi Watanabe, Ayaka Suenaga, Toshiya Kai, Masaki Otagiri, and Toru Maruyama
    • Organizer
      Asian Federation for Pharmaceutical Sciences 2013
    • Place of Presentation
      Ramada Plaza Jeju Hotel(韓国)
    • Related Report
      2013 Research-status Report
  • [Presentation] S-NITROSATED α-1-ACID GLYCOPROTEIN KILLS DRUG-RESISTANT BACTERIA AND AIDS SURVIVAL IN SEPSIS2013

    • Author(s)
      Kaori Watanabe(D3), Yu Ishim, Teruo Kuroda, Wakano Ogawa, Hiroshi Watanabe, Ayaka Suenaga, Toshiya Kai, Masaki Otagiri, Toru Maruyama
    • Organizer
      日本薬物動態学会第28回年会
    • Place of Presentation
      タワーホール船堀
    • Related Report
      2013 Research-status Report
  • [Remarks] 熊本大学薬学部薬剤学分野

    • URL

      http://www.pharm.kumamoto-u.ac.jp/Labs/Yakuzai/

    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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