2019 Fiscal Year Final Research Report
Application for treatments of chronic kidney disease used by podocyte specific transcription factor MafB
Project/Area Number |
19K21330
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Project/Area Number (Other) |
18H06230 (2018)
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund (2019) Single-year Grants (2018) |
Review Section |
0904:Internal medicine of the bio-information integration and related fields
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Research Institution | University of Tsukuba |
Principal Investigator |
Usui Toshiaki 筑波大学, 医学医療系, 講師 (50825099)
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Project Period (FY) |
2018-08-24 – 2020-03-31
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Keywords | 糸球体上皮細胞 / MafB / 転写因子 / 慢性腎臓病 / 巣状分節性糸球体硬化症 / 誘導剤 / atRA |
Outline of Final Research Achievements |
The analysis for an accepted murine model for focal segmental glomerulosclerosis (FSGS), the level of urinary protein in MafB podocyte-specific transgenic (TG) mice was significantly less than in wild-type mice.In addition, the renal damage in TG mice was ameliorated. We already showed that All-trans retinoic acid (atRA), one of vitamin-A derivative, activates Mafb expression in macrophages. We found that atRA induced Mafb expression in cultured murine podocytes in a dose-dependent manner. Next, we investigated the effects of atRA on murine model for FSGS. Glomerular Mafb expression was significantly increased in atRA-treated mice. The level of urinary protein in atRA-treated mice was significantly lower than in atRA-non-treated mice and the renal damage in atRA-treated mice was ameliorated. MafB genetic over expression in podocytes or the MafB inducer protects again FSGS in mice.
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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 |
巣状分節性糸球体硬化症は、指定難病の対象となっている疾患で、治療にはステロイド剤や免疫抑制薬が用いられるが、難治性で、患者の約4割が、発症後15年程度で末期腎不全に至る。主として糸球体上皮細胞の傷害が、巣状分節性糸球体硬化症の発症・進展の鍵を握ると考えられているが、これまで発症メカニズムは十分に解明されていなかった。 今回の研究において、遺伝子操作や既存の白血病治療薬(オールトランスレチノイン酸)投与により、糸球体上皮細胞にMafBを過剰発現させたマウスでは、腎障害悪化やタンパク尿が軽減することを解明した。この結果は、巣状分節性糸球体硬化症の新しい治療法開発の基盤となる。
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