IRF1通过NCOA1/Wnt/β-catenin信号通路调控视网膜缺血-再灌注过程中的自噬和小胶质细胞极化

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2025-03-15 DOI:10.1016/j.cellsig.2025.111746

Di Yang , Jian-shu Kang , Hua Zhong , Hong-mei Liu , Shen Nian , Kai-xiong Qing

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引用次数: 0

摘要

干扰素调节因子1 （interferon regulatory factor 1, IRF1）是眼部发育的重要调节因子，已被证实参与了缺血-再灌注过程的调节。但其在视网膜缺血再灌注（RIR）中的作用尚不清楚。方法采用升高眼压法建立rir大鼠模型。采用苏木精和伊红（HE）染色、免疫荧光（IF）染色和western blot实验探讨RIR中IRF1、自噬和小胶质细胞极化的水平。采用Western blot、透射电镜、IF和ELISA检测，探讨IRF1、核受体共激活因子1 （NCOA1）和Wnt/β-catenin信号通路在OGD/ r诱导的大鼠视网膜小胶质细胞自噬和极化中的作用。CHIP和双荧光素酶实验验证了IRF1和NCOA1之间的相互作用。通过CHIP和双荧光素酶实验验证IRF1和NCOA1之间的相互作用。在大鼠玻璃体内注射干扰IRF1和NCOA1的腺相关病毒，探讨IRF1和NCOA1在RIR大鼠体内的功能。结果RIR大鼠视网膜小胶质细胞sirf1和m1型标志物升高，自噬水平降低。IRF1和NCOA1的下调增加了OGD/ r诱导的视网膜小胶质细胞的自噬，抑制了m1型极化和炎症因子，减轻了大鼠的RIR损伤，抑制了Wnt/β-catenin信号通路的激活。Wnt/β-catenin信号通路激活剂HLY78部分逆转了敲除NCOA1对视网膜小胶质细胞的作用。机制上，IRF1的敲低通过抑制NCOA1的转录抑制Wnt/β-catenin信号通路的激活。结论抑制IRF1通过调节NCOA1/Wnt/β-catenin信号通路对RIR损伤具有保护作用。

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IRF1 regulates autophagy and microglia polarization in retinal ischemia-reperfusion through NCOA1/Wnt/β-catenin signalling pathway

Background

Interferon regulatory factor 1 (IRF1) is an important regulatory factor in the development of eyes, and it has been proved to be involved in the regulation of ischemia-reperfusion process. But its role in retinal ischemia-reperfusion (RIR) remains unclear.

Methods

RIR rat model was induced by increasing intraocular pressure. Hematoxylin and eosin (HE) staining, immunofluorescence (IF) staining, and western blot experiments were used to explore the levels of IRF1, autophagy, and microglia polarization in RIR. Western blot, transmission electron microscope, IF, and ELISA assays were used to explore the effects of IRF1, Nuclear receptor coactivator 1 (NCOA1), and Wnt/β-catenin signalling pathways in OGD/R-induced autophagy and polarization of rat retinal microglia. CHIP and dual-luciferase experiments verify the interaction between IRF1 and NCOA1. CHIP and dual-luciferase experiments were used to verify the interaction between IRF1 and NCOA1. Adeno-associated viruses interfering with IRF1 and NCOA1 were injected into the vitreous of rats to explore the functions of IRF1 and NCOA1 in RIR rats.

Results

IRF1 and M1-type markers of microglia in retina of RIR rats increased, and autophagy level decreased. Knockdown of IRF1 and NCOA1 increased autophagy of OGD/R-induced retinal microglia, inhibited M1-type polarization and inflammatory cytokines, alleviated RIR injury in rats, and inhibited the activation of Wnt/β-catenin signalling pathway. The Wnt/β-catenin signalling pathway activator HLY78 partially reversed the effect of knocking down NCOA1 on retinal microglia. Mechanically, knockdown of IRF1 inhibited the activation of Wnt/β-catenin signalling pathway by inhibiting the transcription of NCOA1.

Conclusion

Inhibition of IRF1 has a protective effect on RIR damage by regulating NCOA1/Wnt/β-catenin signalling pathway.

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来源期刊

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.