Elucidation of the molecular mechanism of advanced glycation ends products on urinary stone formation and exploration of their potential as biomarkers

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16714
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Kanazawa Medical University
• Principal Investigator: INOUE Shinya 金沢医科大学, 医学部, 助教 (20740997)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: High fructose corn syrup / TAGE / 腎臓 / 生活習慣病

Outline of Final Research Achievements

In animal experiments using rats, we analyzed the genetic changes in the kidneys induced by excessive intake of high fructose corn syrup (HFCS) using DNA microarray. We also found that excessive HFCS intake contributed to the increase in serum TAGE and the accumulation of TAGE in liver tissue.Among the genes induced in the kidneys by HFCS, we found that genetic changes in Usp2 and Calb1 were correlated with TAGE in liver tissue.Changes in specific gene expression profiles in the kidney were more correlated with TAGE levels in the liver tissue than in the serum. These findings suggest a direct or indirect interaction may be present between the liver and kidneys that does not involve serum TAGE or RAGE. The involvement of internal signal transduction factors such as exosomes or cytokines is suggested to contribute to the observed changes in kidney gene expression.

Free Research Field

尿路結石症

Academic Significance and Societal Importance of the Research Achievements

果糖ブドウ糖液糖（High Fructose Corn Syrup:HFCS）の過剰摂取が腎臓での遺伝子発現を誘導することを見出した。それらの遺伝子発現は肝臓組織内TAGEと相関し、RAGEを介さないTAGEの直接作用や、メディエーターを介した腎臓と肝臓の間に臓器間ネットワークが存在する可能性が示唆された。これらの結果は、HFCS過剰摂取が体内に及ぼす影響とTAGEを介した生活習慣病発症の解明に意義のある基礎研究である。