2010 Fiscal Year Final Research Report
Development of in vivo evaluation system of human organic anion transpoter
| Project/Area Number |
20390043
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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 Tohoku University, 大学院・医工学研究科, 教授 (80292209)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 腎臓 / トランスポーター / 尿毒症 / 遺伝子改変動物 / プロモーター / SLCO4C1 / スタチン |
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| Research Abstract |
In chronic kidney disease (CKD) patients, the accumulation of uremic toxins causes difficulty in controlling blood pressure, impairs renal function and worsens prognosis. The reduction of accumulated uremic toxins protects against the development of hypertension and ongoing renal damage, but there is no established treatment so far. We have demonstrated that the overexpression of human kidney-specific organic anion transporter SLCO4C1 in rat kidney reduced hypertension, cardiomegaly and inflammation in renal failure together with a reduction of plasma uremic toxins, guanidinosuccinate (GSA), asymmetric dimethylarginine (ADMA) and trans-aconitate. Trans-aconitate is a newly identified uremic toxin.
By transcriptional analysis, we found that the SLCO4C1 transcription is upregulated by various statins. Statins potentate renal proximal function and facilitate excretion of uremic toxins, resulting preventing hypertension and renal inflammation in the renal failure. These data suggest that SLCO4C1 upregulation provides a novel transporter-based therapeutic strategy for CKD patients to reduce renal damage and life-threatening events.
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[Journal Article] Luminal alkalinization attenuates proteinuria-induced oxidative damage in proximal tubular cells.2011
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. 22(4)
Pages: 635-648
Peer Reviewed
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[Journal Article] Metabolomic profiling of uremic solutes in CKD patients.2010
Author(s)
Toyohara T, Akiyama Y, Suzuki T, Takeuchi Y, Mishima E, Tanemoto M, Momose A, Toki N, Sato H, Nakayama M, Hozawa A, Tsuji I, Ito S, Soga T, Abe T.
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Journal Title
Hypertens Res. 33(9)
Pages: 944-952
Peer Reviewed
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[Journal Article] The HMG-CoA reductase inhibitor pravastatin stimulates insulin secretion through organic anion transporter polypeptides.2010
Author(s)
Abe M, Toyohara T, Ishii A, Suzuki T, Noguchi N, Akiyama Y, Shiwaku HO, Nakagomi-Hagihara R, Zheng G, Shibata E, Souma T, Shindo T, Shima H, Takeuchi Y, Mishima E, Tanemoto M, Terasaki T, Onogawa T, Unno M, Ito S, Takasawa S, Abe T.
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Journal Title
Drug Metab Pharmacokinet. 25(3)
Pages: 274-282
Peer Reviewed
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[Journal Article] SLCO4C1 transporter eliminates uremic toxins and attenuates hypertension and renal inflammation.2009
Author(s)
Toyohara T, Suzuki T, Morimoto R, Akiyama Y, Souma T, Shiwaku HO, Takeuchi Y, Mishima E, Abe M, Tanemoto M, Masuda S, Kawano H, Maemura K, Nakayama M, Sato H, Mikkaichi T, Yamaguchi H, Fukui S, Fukumoto Y, Shimokawa H, Inui K, Terasaki T, Goto J, Ito S, Hishinuma T, Rubera I, Tauc M, Fujii-Kuriyama Y, Yabuuchi H, Moriyama Y, Soga T, Abe T.
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Journal Title
J Am Soc Nephrol. 20(12)
Pages: 2546-2555
Peer Reviewed
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