New therapeutic strategy of hypertension in chronic kidney disease by functionally selective modulation of inflammatory signaling via receptor binding molecule

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09293
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Yokohama City University
• Principal Investigator: TAMURA KOUICHI 横浜市立大学, 医学研究科, 教授 (40285143)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 慢性腎臓病 / 高血圧 / 受容体結合因子 / 上皮性ナトリウムチャネル / 炎症性サイトカイン / 分子機序

Outline of Final Research Achievements

We provided evidence that renal ATRAP plays a critical role in suppressing hypertension in a mouse remnant kidney model of chronic kidney disease (CKD). While 129/Sv mice with a remnant kidney showed decreased renal ATRAP expression and developed hypertension, C57BL/6 mice exhibited increased renal ATRAP expression and resistance to progressive hypertension. Consequently, we hypothesized that down-regulation of renal ATRAP expression is involved in pathogenesis of hypertension in CKD. Interestingly, 5/6 nephrectomy in ATRAP-knockout mice on hypertension-resistant C57BL/6 background caused hypertension with increased plasma volume. Moreover, in knockout compared to wild-type C57BL/6 mice after 5/6 nephrectomy, renal expression of the epithelial sodium channel and tumor necrosis factor-α was significantly enhanced. Thus, renal ATRAP down-regulation is involved in the onset and progression of BP elevation in CKD, and it implicates ATRAP as a therapeutic target for hypertension in CKD.

Free Research Field

循環器・腎臓・高血圧内科学