| Journal Title /掲載ジャーナル名 |
Communications Biology |
| Publication Year and Month /掲載年月 |
March, 2025 |
| Paper Title /論文タイトル |
Induction of MASH-like pathogenesis in the Nwd1-/- mouse liver |
| DOI /論文DOI |
10.1038/s42003-025-07717-5 |
| Author of Waseda University /本学の著者 |
SAKAKIBARA, Shinichi(Professor, Faculty of Human Sciences, School of Human Sciences):Correspoinding Author |
| Related Websites /関連Web |
– |
| Abstract /抄録 |
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. |
