論文 - 詳細
| RRC ID | 33257 |
|---|---|
| 著者 | Kwon Y, Song W, Droujinine IA, Hu Y, Asara JM, Perrimon N. |
| タイトル | Systemic organ wasting induced by localized expression of the secreted insulin/IGF antagonist ImpL2. |
| ジャーナル | Dev Cell |
| Abstract |
Organ wasting, related to changes in nutrition and metabolic activity of cells and tissues, is observed under conditions of starvation and in the context of diseases, including cancers. We have developed a model for organ wasting in adult Drosophila, whereby overproliferation induced by activation of Yorkie, the Yap1 oncogene ortholog, in intestinal stem cells leads to wasting of the ovary, fat body, and muscle. These organ-wasting phenotypes are associated with a reduction in systemic insulin/IGF signaling due to increased expression of the secreted insulin/IGF antagonist ImpL2 from the overproliferating gut. Strikingly, expression of rate-limiting glycolytic enzymes and central components of the insulin/IGF pathway is upregulated with activation of Yorkie in the gut, which may provide a mechanism for this overproliferating tissue to evade the effect of ImpL2. Altogether, our study provides insights into the mechanisms underlying organ-wasting phenotypes in Drosophila and how overproliferating tissues adapt to global changes in metabolism. |
| 巻・号 | 33(1) |
| ページ | 36-46 |
| 公開日 | 2015-4-6 |
| DOI | 10.1016/j.devcel.2015.02.012 |
| PII | S1534-5807(15)00114-8 |
| PMID | 25850671 |
| PMC | PMC4437243 |
| MeSH | Animals Animals, Genetically Modified / genetics Animals, Genetically Modified / growth & development Animals, Genetically Modified / metabolism Biomarkers / metabolism Blotting, Western Cells, Cultured Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / genetics Drosophila melanogaster / growth & development Drosophila melanogaster / metabolism Fat Body / cytology Fat Body / metabolism Female Gastrointestinal Tract / cytology Gastrointestinal Tract / metabolism* Gene Expression Profiling Hemolymph / metabolism Hyperglycemia / metabolism Hyperglycemia / pathology Insulin / chemistry* Insulin / metabolism Insulin Secretion Insulin-Like Growth Factor I / antagonists & inhibitors* Insulin-Like Growth Factor I / metabolism Male Metabolomics Muscle, Skeletal / cytology Muscle, Skeletal / metabolism Nuclear Proteins / genetics Nuclear Proteins / metabolism* Oligonucleotide Array Sequence Analysis Ovary / cytology Ovary / metabolism RNA, Messenger / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Stem Cells / cytology Stem Cells / metabolism* Trans-Activators / genetics Trans-Activators / metabolism* Wasting Syndrome / metabolism* Wasting Syndrome / pathology YAP-Signaling Proteins |
| IF | 10.092 |
| 引用数 | 77 |
| WOS 分野 | DEVELOPMENTAL BIOLOGY CELL BIOLOGY |
| リソース情報 | |
| ショウジョウバエ | 15009R-3 |