| 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
|
| リソース情報 |
| 実験動物マウス |
RBRC01828 |
| ヒト・動物細胞 |
HeLa(RCB0007) |
