Blockade of renal malignant cycle by transcriptional regulation of SLCO transporter

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390033
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Tohoku 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
• Keywords: トランスポーター / 尿毒症物質 / GATA / AhR

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.

Research Products

• [Journal Article] Conformational Change in tRNA is an Early Indicator of Acute Cellular Damage with Prognostic Significance (2014)
  • 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
  • Peer Reviewed
• [Journal Article] Indoxyl sulfate down-regulates SLCO4C1 transporter through up-regulation of GATA (2013)
  • Author(s): Akiyama Y., Kikuchi K., Saigusa D., Suzuki T., Takeuchi Y., Mishima E., Yamamoto Y., Ishida A., Sugawara D., Shima H., Toyohara T., Suzuki C., Souma T., Moriguchi T., Tomioka Y., Ito S. and AbeT
  • Journal Title: Plos One Volume: 8 Pages: e66518
  • DOI: 10.1371/journal.pone.0066518
  • Peer Reviewed
• [Journal Article] Mutation of the Mg^<2+> Transporter SLC41A1 Results in a Nephronophthisis-Like Phenotype (2013)
  • Author(s): Hurd TW, Edgar A. 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., AbeT. and Hildebrandt F
  • Journal Title: J. Am. Soc. Nephrol Volume: 24 Pages: 967-977
  • DOI: 10.1681/ASN.2012101034
  • Peer Reviewed
• [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
• [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
• [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
• [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
• [Remarks]
  • URL: http://plaza.umin.ac.jp/~takaabe/
• [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
  • Industrial Property Number: 2013-209539
  • Filing Date: 2013-10-04
• [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
  • Industrial Property Number: JP2013/006916
  • Filing Date: 2013-11-25
  • Overseas