2013 Fiscal Year Final Research Report
Regulation of SLCO4C1 transporter-mediated excretion of uremic toxins as a therapeutic strategy for Chronic Kidney Disease
| Project/Area Number |
24890013
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Medical pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
AKIYAMA Yasutoshi 東北大学, 東北メディカル・メガバンク機構, 非常勤講師 (70635557)
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| Project Period (FY) |
2012-08-31 – 2014-03-31
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| Keywords | トランスポーター / 尿毒症 / 尿毒素 / 慢性腎臓病 |
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| Research Abstract |
Chronic kidney disease (CKD) is a global health problem that carries a substantial risk for cardiovascular morbidity and death. With the progression of CKD, various uremic toxins accumulate, subsequently causing renal damage and hypertension. Recently, we have revealed that kidney-specific organic anion transporter SLCO4C1 excretes uremic toxins, and the up-regulation of SLCO4C1 resulted in the reduction of blood pressure and renal inflammation in a CKD model. In this study, we revealed that indoxyl sulfate (IS), one of the best-known uremic toxins, inhibits the expression of SLCO4C1 through GATA3 and that removal of IS increases the SLCO4C1 expression. The combination therapy of, (1) activating the SLCO4C1 expression by statins, (2) reducing the plasma IS concentration by the administration of AST-120 and (3) administering GATA inhibitor, could be a more effective remedy for the excretion of uremic toxins and preservation of renal function in CKD patients.
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