| 研究課題/領域番号 |
23K15246
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| 研究種目 |
若手研究
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| 配分区分 | 基金 |
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| 審査区分 |
小区分53040:腎臓内科学関連
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| 研究機関 | 金沢大学 |
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研究代表者 |
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| 研究期間 (年度) |
2023-04-01 – 2026-03-31
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| 研究課題ステータス |
交付 (2023年度)
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| 配分額 *注記 |
4,680千円 (直接経費: 3,600千円、間接経費: 1,080千円)
2025年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
2024年度: 1,820千円 (直接経費: 1,400千円、間接経費: 420千円)
2023年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
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| キーワード | bacterial translocation / gut dysbiosis / acute kidney injury |
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| 研究開始時の研究の概要 |
In this study, we test the hypothesis that gut bacteria is involved in the pathogenesis of AKI. We will identify the bacterial translocation and their contribution to AKI. Moreover, we will evaluate the possibility of gut bacteria as a novel biomarker and therapeutic target on AKI.
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| 研究実績の概要 |
In the first year of project, we focused on confirming our hypothesis that gut microbiota may contribute to the pathophysiology of acute kidney injury (AKI). We performed renal unilateral ischemia-reperfusion (IR) in C57BL/6J mice to induce AKI, then investigated evidence of bacterial translocation.
Following the time-course study, we observed an increase in the load of bacteria X load in the feces, suggesting gut dysbiosis after IR induction. We examined and recognized intestinal injuries that could be direct causes of bacterial translocation.We also detected X DNA in the circulation of IR mice, indicating the translocation of bacterial products in AKI mice. By administering fluorescence-labeled X and using multiple immunofluorescence staining, we explored the presence of X in the immune cells (macrophages) and proximal tubules of IR kidneys.
We also investigated the effect of X DNA to the cultured cells and AKI models. The in vitro results showed that a the low amount of X DNA activated bone marrow-derived macrophages (BMDMs) to produce pro-inflammatory cytokines, while a higher concentration of X DNA was required to induce inflammation and injury in kidney tubular cells. Additionally, we confirmed the pathogenic role of X DNA in the AKI condition in vivo. The administration of X DNA augmented renal injuries after IR induction by promoting inflammation.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
This year is the first year we conducted the project as the originally planned and achieved promising and important data. Repeated experiments identified and confirmed key translocated bacteria in AKI mice. We also explored target cells and dose-dependent pathogenic impacts of X DNA in both cultured cells and murine AKI models. These results are new findings and have not been reported until now. Therefore, it is considered that progress is generally going well.
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| 今後の研究の推進方策 |
Next year, we will focus on finding the molecular mechanism to explore the origin and pathways through which X DNA translocates, then activates and accelerates AKI injury. Base on these results, we hope to select and screen potential methods or drugs to prevents AKI progression by targeting X. In addition, we will collect the blood samples of patients with AKI and measure X DNA levels. We will also investigate the correlation of X DNA levels and clinical characteristics to test whether X could be a potential prognostic marker of human AKI.
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