江苏大学学报（医学版）2025，Vol.35Issue(3)：217-229,13.DOI:10.13312/j.issn.1671-7783.y240046
OTUB1基因通过激活SLC7A11信号通路减轻对乙酰氨基酚诱导的急性肝损伤
OTUB1 mitigates acetaminophen-induced acute liver injury by activating the SLC7A11 signaling pathway
摘要
Abstract
Objective:To investigate the function and potential mechanism of OTU domain-containing ubiquitin aldehyde-binding protein 1(OTUB1)gene in acetaminophen(APAP)induced acute liver injury(ALI)and its potential mechanism.Methods:The signaling pathways related to ALI induced by APAP were studied by bioinformatics analysis,and the genes co-expressed with ferroptosis were screened out.Various doses(0,200,300,400 mg/kg)of APAP were intraperitoneally injected into BALB/c mice.The contents of enzymes and cytokines,liver coefficient,expression levels of OTUB1 and solute carrier family 7 member 11(SLC7A11)were detected.HE staining was used to observe the pathological changes of visceral tissues.Finally,OTUB1-overexpressing LO2 and QSG-7701 hepatocyte lines were constructed.The effects of OTUB1 overexpression on APAP-induced liver cell damage were analyzed by detecting cell viability,enzyme and cytokine contents,reactive oxygen species and mitochondrial membrane potential.Results:The results of bioinformatics showed that APAP-induced ALI and acute liver failure intersected with 12 ferroptosis genes,among which the OTUB1 gene,which was significantly downregulated in expression,was included.The results of animal experiments showed that APAP-induced ALI could cause inflammation in mice and down-regulate the expression of OTUB1 and SLC7A11 in a dose-dependent manner.The results of cell experiments showed that LO2 and QSG-7701 hepatocytes with overexpression of OTUB1 attenuate resist cellular inflammation,oxidative stress and mitochondrial damage caused by APAP.Conclusion:The OTUB1 gene may alleviate ALI induced by APAP by activating the SLC7A11 signaling pathway.关键词
含OTU结构域的泛素醛结合蛋白1(OTUB1)/SLC7A11信号通路/对乙酰氨基酚/急性肝损伤/生物信息学分析Key words
OTU domain-containing ubiquitin aldehyde-binding protein 1(OTUB1)/SLC7A11 signal path/acetaminophen/acute liver injury/bioinformatics analysis分类
医药卫生引用本文复制引用
李晓敏,李俊,徐艺珈,贾书冰,赵明沂..OTUB1基因通过激活SLC7A11信号通路减轻对乙酰氨基酚诱导的急性肝损伤[J].江苏大学学报（医学版）,2025,35(3):217-229,13.基金项目
辽宁省自然科学基金面上项目(2022-MS-250) （2022-MS-250）
2022年常州市第九批科技计划项目(应用基础研究指导性)(CJ20229004) （应用基础研究指导性）
