Blockade of renal malignant cycle by transcriptional regulation of SLCO transporter

通过 SLCO 转运蛋白的转录调节阻断肾恶性循环

• 批准号: 23390033
• 负责人: ABE Takaaki
• 金额: $ 11.98万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23390033/
• 关键词: 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

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.

累积的尿毒症毒素抑制各种肾转运蛋白的表达，这种抑制可能进一步降低肾功能，随后引起尿毒症毒素的累积。硫酸吲哚酚（Indoxyl sulfate）是一种强效的尿毒症毒素，可通过转录因子GATA 3直接抑制肾脏特异性有机阴离子转运体SLCO 4C 1的表达。 此外，在5/6肾切除大鼠中，口服吸附剂AST-120治疗显著降低血浆硫酸吲哚酚水平，相反增加slco 4c 1的表达。这些数据表明，去除硫酸吲哚酚并阻断其信号通路可能有助于恢复CKD中SLCO 4C 1介导的尿毒症毒素肾排泄。

项目成果

尿細管排泄機構と尿毒症物質:トランスポーター発現制御による腎不全治療

肾小管排泄机制与尿毒症物质：通过调节转运蛋白表达治疗肾衰竭

• 发表时间: 2010
• 作者: 鈴木健弘;阿部高明
• 通讯作者: 阿部高明

Conformational Change in tRNA is an Early Indicator of Acute Cellular Damage

tRNA 构象变化是急性细胞损伤的早期指标

• 发表时间: 2014
• 期刊: J. Am. Soc. Nephrol.
• 作者: 大羽輝弥;澤田英士;鈴木良明;山村寿男;大矢進;今泉祐治;Mishima E.
• 通讯作者: Mishima E.

Identifying the Uremic Compounds Specifically Involved in the Pathophysiology of Hemodialysis Patients by Capillary Electrophoresis-Mass Spectrometry

通过毛细管电泳-质谱法鉴定专门参与血液透析患者病理生理学的尿毒症化合物

• 发表时间: 2012
• 作者: Akiyama Y;Takeuchi Y;Mishima E;Suzuki T; Ito S;Soga T;Abe T
• 通讯作者: Abe T

Metabolomic profiling of the autosomal dominant polycystic kidney disease rat model

• DOI: 10.1007/s10157-011-0467-4
• 发表时间: 2011-10-01
• 期刊: CLINICAL AND EXPERIMENTAL NEPHROLOGY
• 影响因子: 2.3
• 作者: Toyohara, Takafumi;Suzuki, Takehiro;Abe, Takaaki
• 通讯作者: Abe, Takaaki

甲状腺ホルモン輸送蛋白質

甲状腺激素转运蛋白

• 发表时间: 2010
• 期刊: 日本甲状腺学会雑誌
• 作者: 鈴木健弘;阿部高明
• 通讯作者: 阿部高明