2021 Fiscal Year Final Research Report
Mechanism of TGF-beta-induced podocyte injury and decreased expression of WT1
Project/Area Number |
19K17696
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 53040:Nephrology-related
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Research Institution | Gunma University |
Principal Investigator |
Hamatani Hiroko 群馬大学, 大学院医学系研究科, 助教 (40760658)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | WT1 / アイソフォーム / +KTS/-KTS / 糸球体上皮細胞 / ポドサイト |
Outline of Final Research Achievements |
Wilms' tumour 1 (WT1) gene is essential for normal podocyte function. We examined whether TGF-β, which is involved in podocyte damage, alters the ratio of WT1+KTS/-KTS isoforms by (1) real-time PCR, (2) RNA-Seq, and (3) fragment analysis using DNA sequencers, but no significant changes were observed. The RNA-Seq results suggested that isoforms including +KTS could be important in the recovery of cell morphology after 5 days of TGF-β administration followed by 2 days of incubation without TGF-β. We also searched for the expression of genes that regulate WT1 expression by administration of TGF-β, and the factors that could alter the expression of WT1.
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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 |
我々は糖尿病性腎症やFSGSに関与するTGF-βにより糸球体上皮細胞のWT1の発現が低下することを報告したがその機序は明らかではない。TGF-βによる糸球体上皮細胞障害の機序にWT1+KTS、WT1-KTSのアイソフォームの比率が関与しているか検討したが有意な変化を認めなかった。なお、TGF-β投与後の細胞形態の回復に+KTSアイソフォームが重要な可能性がRNA-Seqの結果から示唆された。また、WT1の発現を制御する遺伝子のTGF-βによる発現変化や、WT1の発現を変化させうる因子の探索をすすめた。今後これらの発現を制御することによりWT1の発現を維持させ治療につながる可能性がある。
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