FOXO1 通过 AKT/Stat3/FOXO1 途径调节 Th17/Treg 比率，减轻肝脏缺血再灌注损伤,Journal of Clinical and Translational Hepatology

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FOXO1 通过 AKT/Stat3/FOXO1 途径调节 Th17/Treg 比率，减轻肝脏缺血再灌注损伤
Journal of Clinical and Translational Hepatology ( IF 3.1 ) Pub Date : 2022-3-15 , DOI: 10.14218/jcth.2021.00551
Hao-Zhen Ren _{1,

2,

3} , Sen-Zhe Xia _{1,

2} , Xue-Qian Qin _{1,

3} , An-Yin Hu ₁ , Jing-Lin Wang _{1,

2,

3}

Affiliation

Background and Aims

手术过程中发生的肝脏缺血再灌注损伤（IRI）严重影响患者的预后。IRI的具体机制尚未完全阐明。本研究旨在探讨肝脏IRI中炎症环境的变化以及Th17/Treg细胞比值与FOXO1表达的关系。

Methods

从患者和小鼠身上采集不同缺血时间的肝脏样本。通过蛋白质印迹和qPCR检测肝脏中炎症标志物和FOXO1的表达。通过流式细胞术分析肝淋巴细胞的表型变化。通过使用 GSK2141795 靶向 AKT 来验证 AKT/Stat3/FOXO1 通路。通过用白藜芦醇上调 FOXO1，证实了 FOXO1 在肝脏炎症和淋巴细胞表型变化中的作用。

Results

缺血时间延长会加重人类和小鼠肝脏 IRI 模型的肝损伤。IR应激通过激活AKT/Stat3/FOXO1信号通路导致Th17/Treg失衡和FOXO1下调。FOXO1 的上调逆转了 Th17/Treg 细胞因子的不平衡并改变了肝脏的炎症环境。

Conclusions

肝脏 IRI 诱导 Th17/Treg 失衡。FOXO1 的上调逆转了这种不平衡并减轻了肝脏炎症。

"点击查看英文标题和摘要"

FOXO1 Alleviates Liver Ischemia-reperfusion Injury by Regulating the Th17/Treg Ratio through the AKT/Stat3/FOXO1 Pathway

Background and Aims

Hepatic ischemic reperfusion injury (IRI) occurring during surgery seriously affects patient prognosis. The specific mechanism of IRI has not been fully elucidated. The study aim was to explore the changes of inflammatory environment, and the relationship of the Th17/Treg cell ratio and FOXO1 expression in hepatic IRI.

Methods

Liver samples at different ischemic times were collected from patients and mice. The expression of inflammatory markers and FOXO1 in the liver was detected by western blotting and qPCR. Phenotypic changes of liver lymphocytes were analyzed by flow cytometry. The AKT/Stat3/FOXO1 pathway was verified by targeting AKT with GSK2141795. The role of FOXO1 in liver inflammation and changes in lymphocyte phenotype was confirmed by upregulating FOXO1 with resveratrol.

Results

Prolonged ischemic time aggravates liver injury in both humans and mouse models of hepatic IRI. IR-stress caused Th17/Treg imbalance and FOXO1 down-regulation by activating the AKT/Stat3/FOXO1 signaling pathway. Upregulation of FOXO1 reversed the Th17/Treg cytokine imbalance and altered the inflammation environment in the liver.

Conclusions

Liver IRI induced Th17/Treg imbalance. Upregulation of FOXO1 reversed the imbalance and alleviated liver inflammation.

更新日期：2022-05-25

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