Hepatic TGFβr1 Deficiency Attenuates Lipopolysaccharide/D-Galactosamine–Induced Acute Liver Failure Through Inhibiting GSK3β–Nrf2–Mediated Hepatocyte Apoptosis and Ferroptosis
Sha Huang, Yuhua Wang, Shuwen Xie, Yuqi Lai, Chan Mo, Ting Zeng, Shanshan Kuang, Guanghui Deng, Chuying Zhou, Yuyao Chen, Shaohui Huang, Lei Gao, Zhiping Lv
Abstract
BACKGROUND & AIMS: Acute liver failure (ALF) is a condition with high mortality and morbidity, characterized by glutathione depletion, oxidative stress, and mitochondrial dysfunction. Ferroptosis may be involved in ALF. Indeed, emerging studies have shown that ferroptosis plays a significant role in ALF. However, the mechanism of ferroptosis in hepatocytes during ALF remains unknown. METHODS: ) mice were generated and subjected to ALF. Electron microscopy was used to detect mitochondrial and other cell substructure changes during ALF. RESULTS: mice compared with its wild-type controls and reversed by ferrostatin-1. CONCLUSIONS: This study shows that TGFβr1 plays a critical role in mediating LPS/D-GalN-induced ALF by promoting apoptosis and ferroptosis.