論文 - 詳細
| RRC ID | 33051 |
|---|---|
| 著者 | Hochmuth CE, Biteau B, Bohmann D, Jasper H. |
| タイトル | Redox regulation by Keap1 and Nrf2 controls intestinal stem cell proliferation in Drosophila. |
| ジャーナル | Cell Stem Cell |
| Abstract |
In Drosophila, intestinal stem cells (ISCs) respond to oxidative challenges and inflammation by increasing proliferation rates. This phenotype is part of a regenerative response, but can lead to hyperproliferation and epithelial degeneration in the aging animal. Here we show that Nrf2, a master regulator of the cellular redox state, specifically controls the proliferative activity of ISCs, promoting intestinal homeostasis. We find that Nrf2 is constitutively active in ISCs and that repression of Nrf2 by its negative regulator Keap1 is required for ISC proliferation. We further show that Nrf2 and Keap1 exert this function in ISCs by regulating the intracellular redox balance. Accordingly, loss of Nrf2 in ISCs causes accumulation of reactive oxygen species and accelerates age-related degeneration of the intestinal epithelium. Our findings establish Keap1 and Nrf2 as a critical redox management system that regulates stem cell function in high-turnover tissues. |
| 巻・号 | 8(2) |
| ページ | 188-99 |
| 公開日 | 2011-2-4 |
| DOI | 10.1016/j.stem.2010.12.006 |
| PII | S1934-5909(10)00701-0 |
| PMID | 21295275 |
| PMC | PMC3035938 |
| MeSH | Animals Cell Proliferation Drosophila Drosophila Proteins / genetics Drosophila Proteins / metabolism* Intestines / cytology* Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism* Kelch-Like ECH-Associated Protein 1 Microscopy Models, Biological NF-E2-Related Factor 2 / genetics NF-E2-Related Factor 2 / metabolism* Oxidation-Reduction Reactive Oxygen Species / metabolism Stem Cells / cytology* Stem Cells / metabolism |
| IF | 20.86 |
| 引用数 | 192 |
| WOS 分野 | CELL & TISSUE ENGINEERING CELL BIOLOGY |
| 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 | F1000Research |
| 各媒体での言及数の合計 | 2 |
| 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 | |
| ショウジョウバエ | 2286R-2 2286R-3 6343R-1 6343R-2 |