Blockade of renal malignant cycle by transcriptional regulation of SLCO transporter
| Project/Area Number |
23390033
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
ABE Takaaki 東北大学, 医工学研究科, 教授 (80292209)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| 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)
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| 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.
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Report
(4 results)
Research Products
(46 results)
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[Journal Article] Indoxyl sulfate down-regulates SLCO4C1 transporter through up-regul ation 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.
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Journal Title
PLoS One
Volume: 8
Issue: 7
Pages: e66518-e66518
DOI
Related Report
Peer Reviewed
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[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
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Journal Title
J Am Soc Nephrol.
Volume: 24
Issue: 6
Pages: 967-977
DOI
Related Report
Peer Reviewed
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[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
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Journal Title
Clin Exp Nephrol
Volume: 15
Pages: 676-87
Related Report
Peer Reviewed
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[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
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Journal Title
J Am Soc Nephrol
Volume: 22
Pages: 635-48
Related Report
Peer Reviewed
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[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
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