Development of novel drugs for CKD

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293031
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• 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): 2014-04-01 – 2017-03-31
• Keywords: トランスポーター / SLCO4C1 / 尿毒素 / 腎不全 / インドール

Outline of Final Research Achievements

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. Recently, we have revealed that human 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. We revealed that the uremic toxin transporter, SLCO4C1, is negatively regulated by a representative uremic toxin indoxyl sulfate, through a transcription factor GATA3. The removal of indoxyl sulfate and blocking its signaling pathway should be an effective strategy to restore the SLCO4C1-mediated renal excretion of uremic toxins.
In addition, among uremic toxins, indole-3-acetic acid significantly increased the cellular ATP level in Hep3B human cells. Indole derivatives may represent a novel therapeutic strategy for treating AKI and CKD as a mitochondria-homing drug.

Free Research Field

腎臓内科