Supression Thioredoxin reductase 3 exacerbates the progression of liver cirrhosis via activation of ferroptosis pathway

文献类型： 外文期刊

第一作者： Liu, Qi

作者： Liu, Qi;Xu, Liming;Ren, Guangming;Zhao, Jingzhuang;Shao, Yizhi;Lu, Tongyan;Lu, Tongyan

作者机构：

关键词： Liver cirrhosis; Txnrd3; Thiacetamide; Ferroptosis; Iron overload

期刊名称：LIFE SCIENCES （ 影响因子：6.1； 五年影响因子：5.8 ）

ISSN： 0024-3205

年卷期： 2023 年 321 卷

页码：

收录情况： SCI

摘要： Aims: In the past decades, Txnrd3 as selenoprotein is considered to be highly expressed in testis and participate in sperm mature; however its role in liver diseases needs further study. Iron is essential for humans and animals, while its overload could damage to multiple organs. However, role of Txnrd3 and iron in cirrhosis is still unclear. Materials and methods: Forty 8-week-old wild-type and forty Txnrd3-/-mice were selected to build liver cirrhosis model using Thiacetamide solution, deposition of iron in liver was observed via Prussian blue staining. Txnrd3 overexpression/knockdown model in vitro was constructed based on cell transfection techniques in AML12 cells, expression abundance of ferroptosis pathway genes within cells and tissues were determined by qRT-PCR and Western Blot. Key findings: Results showed that Txnrd3-/-mice developed more pronounced liver damage, accompanied by reduced GPX4 expression and iron deposition. A significant decrease in the expression abundance of GPX4 was also detected in Txnrd3 knock-down AML12 cells. In summary, Txnrd3 knockdown could result in iron overload and ferroptosis pathway activation within liver tissues and hepatocytes, ultimately lead to the occurrence of liver injury and cirrhosis. Significance: These results will provide biological markers for early diagnosis during cirrhosis and lay a theo-retical basis for clinical therapy.

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