转铁蛋白
肝硬化
四氯化碳
内科学
肝功能
内分泌学
血色病
四氯化碳
纤维化
肝纤维化
脂质过氧化
转铁蛋白受体
平衡
生物
氧化应激
肝细胞
化学
免疫学
医学
生物化学
体外
有机化学
作者
Yingying Yu,Li Jiang,Hao Wang,Zhe Shen,Qi Cheng,Pan Zhang,Jiaming Wang,Qian Wu,Xuexian Fang,Lingyan Duan,Shufen Wang,Kai Wang,Peng An,Tuo Shao,Raymond T. Chung,Shusen Zheng,Junxia Min,Fudi Wang
出处
期刊:Blood
[American Society of Hematology]
日期:2020-05-07
卷期号:136 (6): 726-739
被引量:389
标识
DOI:10.1182/blood.2019002907
摘要
Abstract Although the serum-abundant metal-binding protein transferrin (encoded by the Trf gene) is synthesized primarily in the liver, its function in the liver is largely unknown. Here, we generated hepatocyte-specific Trf knockout mice (Trf-LKO), which are viable and fertile but have impaired erythropoiesis and altered iron metabolism. Moreover, feeding Trf-LKO mice a high-iron diet increased their susceptibility to developing ferroptosis-induced liver fibrosis. Importantly, we found that treating Trf-LKO mice with the ferroptosis inhibitor ferrostatin-1 potently rescued liver fibrosis induced by either high dietary iron or carbon tetrachloride (CCl4) injections. In addition, deleting hepatic Slc39a14 expression in Trf-LKO mice significantly reduced hepatic iron accumulation, thereby reducing ferroptosis-mediated liver fibrosis induced by either a high-iron diet or CCl4 injections. Finally, we found that patients with liver cirrhosis have significantly lower levels of serum transferrin and hepatic transferrin, as well as higher levels of hepatic iron and lipid peroxidation, compared with healthy control subjects. Taken together, these data indicate that hepatic transferrin plays a protective role in maintaining liver function, providing a possible therapeutic target for preventing ferroptosis-induced liver fibrosis.
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