Understanding the physiological regulatory mechanisms and pathophysiological processes of uromodulin

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08249
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Mori Takayasu 東京医科歯科大学, 東京医科歯科大学病院, 助教 (00735813)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ウロモジュリン / 高血圧症 / ADTKD / 遺伝子解析研究 / 次世代シークエンサー / CFAP47 / ADPKD

Outline of Final Research Achievements

We are continuing our research activities aimed at elucidating the genetic background of chronic kidney disease (CKD) and exploring treatment methods by utilizing a comprehensive CKD gene panel test constructed independently using next-generation sequencing (NGS). Focusing on UMOD (uromodulin), a common risk gene for CKD and a cause of rare kidney diseases, we discovered and reported that vasopressin plays an important role in the physiological stimulation of UMOD tubular secretion, which had previously been unexplained. Concurrently, genetic analysis of 90 chronic maintenance dialysis patients revealed that 11% had hereditary kidney diseases, identified CFAP47 as a new causative gene for polycystic kidney disease, and found that approximately 40% of CKD cases with a family history were due to Alport syndrome.

Free Research Field

腎臓病遺伝子解析

Academic Significance and Societal Importance of the Research Achievements

本研究は、次世代シーケンサー（NGS）を用いた網羅的な腎臓病（CKD）遺伝子解析研究を通じて、CKDの遺伝的背景を解明し、新たな治療法の探索を目指している。特に、CKDと関わりの深いUMODの生理的役割の解明はCKDの病態理解を深める重要な知見として期待される。また、パネル遺伝子解析は早期の正確な診断や個別化医療の推進、ひいてはCKD患者の予後改善や新規治療法の開発にも貢献し、大きな社会的意義を持つと考えられる。