earch for "the true uremic substance" focusing on membrane transporters of monocytes and elucidation of the exacerbation mechanism of CKD-induced heart failure

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K21220
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0909:Sports sciences, physical education, health sciences, and related fields
• Research Institution: Kyushu University
• Principal Investigator: Yoshida Yuya 九州大学, 薬学研究院, 助教 (90907536)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 慢性腎臓病 / ビタミンA / 体内時計 / トランスポーター

Outline of Final Research Achievements

Chronic kidney disease (CKD) patients suffer from various diseases due to accumulation of uremic substances in the body. Inspired by our previous findings of "increased cellular uptake of retinol, a uremic substance," we searched for membrane transporters responsible for the uptake of other uremic substances in monocytes of CKD mice and identified "true uremic substances" that strongly correlate with the pathophysiology of CKD. We identified several candidate membrane molecules based on NGS analysis, and in particular, identified transporters with marked changes in expression and substances that are taken up into cells via these transporters. The uptake of these substances was significantly increased in CKD, and they were involved in the increased expression of ALDH and other enzymes that metabolize reactive oxygen species.

Free Research Field

生命科学、時間生物学

Academic Significance and Societal Importance of the Research Achievements

本研究で同定した物質は、CKD時に排泄が阻害されることは以前から知られていたが、この分子自体には一般に毒性はない、と考えられており、CKD時の病態悪化の原因としては着目されてこなかった。本研究による解析にて、この物質の細胞内での異常な蓄積が炎症の増悪に寄与していることを明らかにした。本物質が「真の尿毒症物質」として着目されるきっかけとなることが期待される。