Abstract：
Glutaredoxin 2 (Grx2), a mitochondrial glutathione-dependent oxidoreductase, is crucial for maintaining redox homeostasis and cellular functions in the lens. The oxidative stress-induced epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is related to posterior capsule opacification. In this study, we investigated the effects of Grx2 on oxidative stress-induced EMT in LECs during posterior capsule opacification. We found that Grx2 expression was substantially decreased during the EMT of LECs and in a mouse model of cataract surgery. Deletion of Grx2 aggravated the generation of reactive oxygen species, including those that are mitochondria-derived, and promoted the proliferation and EMT of the LECs. This was reversed by Grx2 overexpression. In vivo, proteomic liquid chromatography-mass spectrometry analysis showed that integrin-linked kinase (ILK) was significantly upregulated in the lens posterior capsule of a Grx2 knockout (KO) mouse model. Compared with that of the wild-type group, the expression of ILK and EMT markers was increased in the Grx2 KO group which was reversed in the Grx2 knock-in group. Inhibition of ILK partially blocked Grx2 knockdown-induced EMT and prevented the increased phosphorylation of Akt and GSK-3β and the nuclear translocation of β-catenin in the Grx2 KO group. Finally, inhibition of the Wnt/β-catenin pathway partially blocked the Grx2 knockdown-induced EMT. In conclusion, we demonstrated that Grx2 protects LECs from oxidative stress-related EMT by regulating the ILK/Akt/GSK-3β axis.
摘要：
谷氧还蛋白2(Grx2),线粒体谷胱甘肽依赖性氧化还原酶，对于维持晶状体中的氧化还原稳态和细胞功能至关重要。氧化应激诱导的晶状体上皮细胞（LECs）上皮间质转化（EMT）与后囊混浊有关。在这项研究中,我们研究了Grx2对后囊混浊过程中LECs中氧化应激诱导的EMT的影响.我们发现Grx2表达在LEC的EMT期间和在白内障手术的小鼠模型中显著降低。Grx2的缺失加剧了活性氧的产生，包括那些来自线粒体的，并促进了LECs的增殖和EMT。这被Grx2过表达逆转。在体内,蛋白质组学液相色谱-质谱分析显示，整合素连接激酶（ILK）在Grx2敲除（KO）小鼠模型的晶状体后囊中明显上调。与野生型组相比，Grx2KO组中ILK和EMT标志物的表达增加，而Grx2敲入组中则相反。ILK的抑制部分阻断了Grx2敲低诱导的EMT，并阻止了Grx2KO组中Akt和GSK-3β的磷酸化增加以及β-catenin的核易位。最后,Wnt/β-catenin通路的抑制部分阻断了Grx2敲低诱导的EMT。总之,我们证明Grx2通过调节ILK/Akt/GSK-3β轴保护LEC免受氧化应激相关的EMT。
