論文 - 詳細
| RRC ID | 83305 |
|---|---|
| 著者 | Yamada S, Ogawa H, Funato M, Kato M, Nakadate K, Mizukoshi T, Kawakami K, Kobayashi R, Horii T, Hatada I, Sakakibara SI. |
| タイトル | Induction of MASH-like pathogenesis in the Nwd1-/- mouse liver. |
| ジャーナル | Commun Biol |
| Abstract |
Endoplasmic reticulum (ER) stores Ca2+ and plays crucial roles in protein folding, lipid transfer, and it's perturbations trigger an ER stress. In the liver, chronic ER stress is involved in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). Dysfunction of sarco/endoplasmic reticulum calcium ATPase (SERCA2), a key regulator of Ca2+ transport from the cytosol to ER, is associated with the induction of ER stress and lipid droplet formation. We previously identified NACHT and WD repeat domain-containing protein 1 (Nwd1) localized at the ER and mitochondria. However, the physiological significance of Nwd1 outside the brain remains unclear. In this study, we revealed that Nwd1-/- mice exhibited pathological manifestations comparable to MASH. Nwd1 interacts with SERCA2 near ER membranes. Nwd1-/- livers exhibited reduced SERCA2 ATPase activity and a smaller Ca2+ pool in the ER, leading to an exacerbated state of ER stress. These findings highlight the importance of SERCA2 activity mediated by Nwd1 in the pathogenesis of MASH. |
| 巻・号 | 8(1) |
| ページ | 348 |
| 公開日 | 2025-3-11 |
| DOI | 10.1038/s42003-025-07717-5 |
| PII | 10.1038/s42003-025-07717-5 |
| PMID | 40069352 |
| PMC | PMC11897295 |
| MeSH | Animals Calcium / metabolism Endoplasmic Reticulum / metabolism Endoplasmic Reticulum Stress Fatty Liver* / genetics Fatty Liver* / metabolism Fatty Liver* / pathology Liver* / metabolism Liver* / pathology Male Mice Mice, Inbred C57BL Mice, Knockout Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism |
| 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 | News |
| 各媒体での言及数の合計 | 19 |
| 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 | |
| 実験動物マウス | RBRC01828 |
| ヒト・動物細胞 | HeLa(RCB0007) |