The Emerging Role of Ferroptosis in Liver Diseases.

The Emerging Role of Ferroptosis in Liver Diseases.
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铁凋亡在肝脏疾病中的新兴作用。

DOI:
10.3389/fcell.2021.801365
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发表时间:
2021
影响因子:
5.5
通讯作者:
Zhai YZ
Zhai YZ
中科院分区:
生物学2区
文献类型:
--
作者:
Chen S;Zhu JY;Zang X;Zhai YZ

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铁凋亡是一种新发现的由铁依赖性脂质过氧化物介导的细胞死亡类型。铁代谢紊乱、氨基酸抗氧化系统失衡和脂质过氧化物蓄积被认为是铁缺乏症的独特特征。近年来,由于其参与各种疾病,包括癌症、肾损伤和神经退行性疾病,铁凋亡的失调已被深入研究。值得注意的是,越来越多的证据表明,铁凋亡在广泛的肝脏疾病中起着不同的作用。一方面,抑制铁凋亡可以抵消几种肝脏疾病的病理生理学进展,如酒精性肝损伤、非酒精性脂肪变性肝炎和纤维化。另一方面,诱导铁凋亡可能会限制对目前肝细胞癌(HCC)治疗药物(如索拉非尼)的继发性耐药的出现。在此,我们总结了肝脏疾病中涉及的铁凋亡的生物学特性和调节信号通路。本文还对目前应用于肝脏疾病的铁凋亡诱导剂或抑制剂进行了综述。这项工作旨在为肝脏疾病的发病机制和治疗方法的新兴作用提供新的见解。
Ferroptosis is a newly discovered type of cell death mediated by iron-dependent lipid peroxide. The disturbance of iron metabolism, imbalance of the amino acid antioxidant system, and lipid peroxide accumulation are considered distinct fingerprints of ferroptosis. The dysregulation of ferroptosis has been intensively studied in recent years due to its participation in various diseases, including cancer, kidney injury, and neurodegenerative diseases. Notably, increasing evidence indicates that ferroptosis plays different roles in a wide spectrum of liver diseases. On the one hand, inhibiting ferroptosis may counteract the pathophysiological progression of several liver diseases, such as alcoholic liver injury, nonalcoholic steatosis hepatitis and fibrosis. On the other hand, inducing ferroptosis may restrict the emergence of secondary resistance to current medicines, such as sorafenib, for hepatocellular carcinoma (HCC) therapy. Here, we summarize the biological characteristics and regulatory signalling pathways of ferroptosis involved in liver disease. The current available medical agents targeting ferroptosis, including inducers or inhibitors applied in liver diseases, are also reviewed. This work aims to provide new insight into the emerging role of pathogenesis and therapeutic approaches for liver diseases.
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