| Project/Area Number |
18K08226
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | Nihon University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | HCaRG / COMMD5 / 急性腎障害 / 尿細管上皮バリア / E-cadherin / ミトコンドリア / リソソーム分解系 / 腎保護 / オートファジーフラックス / 上皮細胞バリア / 尿細管上皮細胞 / 間葉上皮移行 |
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| Outline of Final Research Achievements |
Hypertension-related, calcium-regulated gene (HCaRG/COMMD5) is highly expressed in renal proximal tubules and accelerates tubular repair by facilitating re-differentiation of injured tubular cells. In this study, we demonstrated that the renal tubular epithelial barrier function was maintained by HCaRG via increasing E-cadherin expression and/or facilitating its reutilization even when epithelial cells were exposed to cisplatin and hydrogen peroxide. Consequently, mitochondrial dysfunction was mitigated and the autophagic-lysosomal system was enhanced in injured renal epithelial cells. In the cisplatin-induced acute kidney injury (AKI), HCaRG overexpression in renal tubules of mice prevented renal dysfunction, and reduced apoptosis and interstitial morphological damages. These data suggest that HCaRG prevents AKI by the maintaining of a renal tubular epithelial barrier function and by enhancing intracellular degradation systems.
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| Academic Significance and Societal Importance of the Research Achievements |
上皮細胞は、生体内の内部環境と外部環境を隔て、生体の恒常性を維持する役割を担っている。現在、皮膚や消化管などの上皮細胞間バリア機構ついて多くの報告がされているが、腎臓についてはまだ少ない。HCaRGは、細胞間接着因子であるE-cadherinを増加させ、尿細管上皮細胞の細胞間構造の形成を促す遺伝子である。今回、HCaRGによる上皮細胞間バリア増強作用により、薬剤性急性腎障害による尿細管上皮細胞の細胞死や組織障害が抑制され、腎機能が保護されることが明らかになった。今後、HCaRGを標的とした新たな腎臓病の治療法や予防法へと応用でき、透析導入患者を減らし、医療費の削減へ繋がると期待される。
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