2021 Fiscal Year Final Research Report
Elucidation of underlying mechanism of the onset and renal deterioration of kidney disease contributed by lipid chaperones
| Project/Area Number |
19K08708
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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 | Sapporo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
古橋 眞人 札幌医科大学, 医学部, 講師 (20563852)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | FABP4 / 慢性腎臓病 / 脂質代謝異常症 / 脂質シャペロン / 糸球体内皮細胞 / 糸球体上皮細胞 / 尿バイオマーカー / lipid nephrotoxicity |
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| Outline of Final Research Achievements |
In a renal biopsy cohort, urinary FABP4 excretion was associated with renal function, urinary protein levels and deterioration of renal function after 1 year. In a general population cohort, a high LDL-cholesterol level was negatively associated with change in eGFR during 10-year follow-up period and was a risk factor for the development of CKD in males. In IgA nephropathy and gddY, a IgAN-prone mouse model, expression of FABP4 was ectopically induced by glomerular injury in cells of the glomerulus including glomerular endothelial cells and macrophages, and the extent of glomerular FABP4 expression was associated with proteinuria and renal dysfunction. Expression of ER stress markers were present on the cells in glomerulus in IgAN and in gddY. In human renal glomerular endothelial cells, FABP4 was induced by treatment with VEGF and was secreted from cells. Treatment of podocytes with FABP4 significantly increased gene expression of inflammatory cytokines and ER stress markers.
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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 |
脂質代謝異常は腎障害の原因である。本研究では障害された糸球体に脂質シャペロンの一つであるFABP4の新規発現が誘導され、尿FABP4排泄量は糸球体FABP4発現量を反映することが、その分子生物学的メカニズムの一端を含め明らかになった。また尿FABP4排泄量は糸球体障害マーカーとして腎臓病早期発見のみならず、腎疾患症例の診断予測ならびに腎障害進行予測に有用である可能性が示され、今後の腎診療に対する役割が期待される。心血管疾患発症や新型コロナウイルス感染症重症化に関わる肥満などの代謝異常と腎臓病は現代人の重要な公衆衛生上の課題であり、FABP4が介在する代謝異常と腎障害の解明には社会的意義がある。
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