論文 - 詳細
| RRC ID | 81495 |
|---|---|
| 著者 | Gera J, Kumar D, Chauhan G, Choudhary A, Rani L, Mandal L, Mandal S. |
| タイトル | High sugar diet-induced fatty acid oxidation potentiates cytokine-dependent cardiac ECM remodeling. |
| ジャーナル | J Cell Biol |
| Abstract |
Context-dependent physiological remodeling of the extracellular matrix (ECM) is essential for development and organ homeostasis. On the other hand, consumption of high-caloric diet leverages ECM remodeling to create pathological conditions that impede the functionality of different organs, including the heart. However, the mechanistic basis of high caloric diet-induced ECM remodeling has yet to be elucidated. Employing in vivo molecular genetic analyses in Drosophila, we demonstrate that high dietary sugar triggers ROS-independent activation of JNK signaling to promote fatty acid oxidation (FAO) in the pericardial cells (nephrocytes). An elevated level of FAO, in turn, induces histone acetylation-dependent transcriptional upregulation of the cytokine Unpaired 3 (Upd3). Release of pericardial Upd3 augments fat body-specific expression of the cardiac ECM protein Pericardin, leading to progressive cardiac fibrosis. Importantly, this pathway is quite distinct from the ROS-Ask1-JNK/p38 axis that regulates Upd3 expression under normal physiological conditions. Our results unravel an unknown physiological role of FAO in cytokine-dependent ECM remodeling, bearing implications in diabetic fibrosis. |
| 巻・号 | 223(9) |
| 公開日 | 2024-9-2 |
| DOI | 10.1083/jcb.202306087 |
| PII | 276823 |
| PMID | 38916917 |
| PMC | PMC11199913 |
| MeSH | Animals Cytokines / genetics Cytokines / metabolism Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Drosophila melanogaster / metabolism Extracellular Matrix* / metabolism Fatty Acids* / metabolism Fibrosis / metabolism MAP Kinase Signaling System Myocardium / metabolism Myocardium / pathology Oxidation-Reduction* Pericardium / metabolism Pericardium / pathology Reactive Oxygen Species / metabolism Transcription Factors / genetics Transcription Factors / metabolism |
| IF | 8.811 |
| 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 | 60 |
| 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 | DGRC#116261 DGRC#116262 |