2022 Fiscal Year Final Research Report
Pathophysiological roles of cell senescence related gene in the polycystic kidney disease
Project/Area Number |
20K08583
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53040:Nephrology-related
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Research Institution | Chiba University |
Principal Investigator |
Hatano Ryo 千葉大学, 大学院医学研究院, 助教 (60521713)
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Co-Investigator(Kenkyū-buntansha) |
伊藤 素行 千葉大学, 大学院薬学研究院, 教授 (20377906)
三木 隆司 千葉大学, 大学院医学研究院, 教授 (50302568)
Wiriyasermkul Pattama 東京慈恵会医科大学, 医学部, 助教 (80825836)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 細胞増殖 / 多発性嚢胞腎 |
Outline of Final Research Achievements |
Zfp277 was previously identified as a cell senescence associated transcriptional factor. By contrast, recent study revealed that the expression of Zfp277 is enhanced in actively proliferating cells, suggesting that Zfp277 plays distinct roles in different types of cells. In this study, we focus on the functional role of renal Zfp277 since it is highly expressed in the kidney. We observed that renal Zfp277 expression was upregulated in several animal models such as acute kidney injury (AKI) and polycystic kidney disease (PKD), suggesting that tubular Zfp277 expression is associated with the tubular cell proliferation. On the other hand, we discovered that numbers of pancreatic islet in adult Zfp277 knockout mice are significantly lower than wild type mice, suggesting that Zfp277 regulates islet cell growth. Our findings suggest that Zfp277 plays physiologically important roles in the regulation of cell proliferation and adaptive response to cell injury.
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Free Research Field |
腎生理学
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Academic Significance and Societal Importance of the Research Achievements |
本研究において、転写因子の一種であるZfp277が生体内において細胞増殖を伴うような事象において発現が誘導され、組織の成熟や組織傷害に対する代償機構に関与することが明らかになった。生体の機能恒常性維持機能の一部としてZfp277は膵頭の成熟に寄与し成体における糖代謝恒常性の維持に寄与すると考えられ、その機能障害は糖尿病の発症リスクとなりうる。一方で、組織障害時の発現上昇は組織の修復過程で重要な役割を果たす可能性が考えられる。Zfp277の発現上昇は多発性嚢胞腎における細胞増殖にも寄与するものと考えられ、機能を制御することにより疾患の治療にも応用できることが期待される。
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