論文 - 詳細
| RRC ID | 78188 |
|---|---|
| 著者 | Aihara S, Torisu K, Uchida Y, Imazu N, Nakano T, Kitazono T. |
| タイトル | Spermidine from arginine metabolism activates Nrf2 and inhibits kidney fibrosis. |
| ジャーナル | Commun Biol |
| Abstract |
Kidney metabolism may be greatly altered in chronic kidney disease. Here we report that arginine metabolism is the most altered in unilateral ureteral obstruction (UUO)-induced fibrosis of the kidneys in metabolomic analysis. Spermidine is the most increased metabolite of arginine. In human glomerulonephritis, the amount of spermidine shown by immunostaining is associated with the amount of fibrosis. In human proximal tubule cells, spermidine induces nuclear factor erythroid 2-related factor 2 (Nrf2). Subsequently, fibrotic signals, such as transforming growth factor β1 secretion, collagen 1 mRNA, and oxidative stress, represented by a decrease in the mitochondrial membrane potential is suppressed by spermidine. UUO kidneys of Arg2 knockout mice show less spermidine and significantly exacerbated fibrosis compared with wild-type mice. Nrf2 activation is reduced in Arg2 knockout UUO kidneys. Spermidine treatment prevents significant fibrotic progression in Arg2 knockout mice. Spermidine is increased in kidney fibrosis, but further increases in spermidine may reduce fibrosis. |
| 巻・号 | 6(1) |
| ページ | 676 |
| 公開日 | 2023-6-28 |
| DOI | 10.1038/s42003-023-05057-w |
| PII | 10.1038/s42003-023-05057-w |
| PMID | 37380734 |
| PMC | PMC10307812 |
| MeSH | Animals Arginine Fibrosis Humans Kidney Mice Mice, Knockout NF-E2-Related Factor 2 / genetics Renal Insufficiency, Chronic* Spermidine / pharmacology Ureteral Obstruction* / complications |
| IF | 4.165 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 12 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Atg5^(+/+)MEF(RCB2710) Atg5^(-/-)MEF(RCB2711) |