Suppression of PRDX4 inhibits cell proliferation and invasion of ectopic endometrial stromal cells in endometriosis

Abstract

Oxidative stress (OS) has been proposed to play a role in the development of EMs. Peroxiredoxins are a family of antioxidant proteins that exhibit peroxidase activity in a thioredoxin-dependent manner, protecting cells against OS. The Western blotting results showed that the relative expression of PRDX4 was significantly increased in ectopic endometria compared with the normal endometria of EMs-free (p < .05). The H₂O₂ concentration was also significantly higher in the ectopic endometrium. PRDX4 siRNA was transfected into primary ectopic endometrial stromal cells (EESCs). The viability of the transfected EESCs was measured by CCK-8 assay, and the results showed significantly decreased cell viability. Furthermore, the apoptosis rate and ROS generation in flow cytometry assays were significantly increased after the knockdown of PRDX4 expression (p < .05). Scratch assays and transwell assays revealed that decreased expression of PRDX4 mediated by siRNA inhibited EESC migration and invasion. In conclusion, these findings indicate the potential role of PRDX4 in the development of EMs and PRDX4 as a possible therapeutic target for EMs treatment.

Chinese abstract

氧化应激（OS）已被认为在EMs的发展中发挥作用。硫氧还蛋白过氧化物酶是一类抗氧化蛋白, 以硫氧还蛋白依赖性的方式表现出过氧化物酶的活性, 从而保护细胞免受OS的伤害。Western blotting的结果显示, 与无EMs的正常子宫内膜相比, 异位子宫内膜中的PRDX4的相对表达明显增加（p<0.05）。异位子宫内膜的H₂O₂的浓度也显著增高。将PRDX4的siRNA转染到原代异位子宫内膜基质细胞（EESCs）中。CCK-8法测定转然后EESCs的细胞活力, 结果显示细胞活力明显下降。此外, PRDX4表达下调后, 流式细胞术检测细胞凋亡率和ROS生成显著增加（p<0.05）。Scratch和Transwell实验结果显示, siRNA介导的PRDX4表达降低抑制了EESC的迁移和侵袭。综上所述, 这些发现表明PRDX4在EMs发展过程中的潜在作用, PRDX4可能作为EMs治疗的靶点。

Keywords:

• Endometrial stromal cells
• peroxiredoxins 4
• ROS
• proliferation
• invasion

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Natural Science Foundation of Jiangxi Province under Grant [20151BAB215042, 20181BAB215009]; Key Research and Development Program of Jiangxi Province under Grant [20161BBG70138]; the National Natural Science Foundation of China under Grant [81660736].