2022 Fiscal Year Final Research Report
Study of the Sialic Acid Modification and Kdn Accumulation in Acquired Cystic Kidney Disease
Project/Area Number |
19K17730
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 53040:Nephrology-related
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Research Institution | University of Tsukuba |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Keywords | 後天性嚢胞腎 / 後天性嚢胞腎随伴腎細胞癌 / シアル酸 / Kdn / バイオマーカー |
Outline of Final Research Achievements |
Acquired cystic kidney disease (ACKD), a non-hereditary cystic disease, occurs in kidneys of choronic kidney disease (CKD) patients. The frequency of renal cell carcinoma is 5- to 15-fold higher in hemodialysis patients than in non-hemodialysis patients, and the frequency of acquired cystic kidney-associated renal cell carcinoma (ACD-RCC) is known to increase with the number of years of dialysis. Accoding to the discoveries of deaminoneuraminic acid (Kdn) accumulation in hemodialysis patients, and the presence of anti-Kdn antibodies in human serum, we hypothesized that Kdn is involved in the development of ACKD and ACD-RCC. We established a method to detect Kdn-conjugated glycopeptides in patient tissues and cell cultures. Although we could not find Kdn-conjugated glycopeptides in ACD-RCC tissues, we found several unique sialylated peptides that could be usuful biomarkers for ACD-RCC.
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Free Research Field |
腎臓内科学
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Academic Significance and Societal Importance of the Research Achievements |
透析患者のKdn蓄積とヒト血清中に抗Kdn抗体が存在するという発見から、ACKDのACD-RCCへの進展メカニズム解明を目指し、Kdn探索を行った。研究を通して、ACD-RCC組織からKdn型ペプチドを発見することはできなかったが、ヒト細胞株上でKdn型ペプチドを検出する手法を確立できた意義は大きい。また、研究期間中に米国での事前検討を深化させ、脊椎動物が保存するマンノース代謝経路とKdn産生の意義は過剰なマンノースの緩衝機構にあるとする学説を論文化できた。また研究の過程で透析腎癌マーカーとして有力な分子を複数発見し特許出願した社会的意義は大きく、検証のための多施設共同研究を開始できている。
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