Department 3 of Obstetrics, Cangzhou Central Hospital, Cangzhou, Hebei, China.
Immun Inflamm Dis. 2021 Sep;9(3):1016-1024. doi: 10.1002/iid3.465. Epub 2021 Jun 5.
Preeclampsia can cause severe consequences for pregnant women and infants, and developing effective medicine or methods to prevent or treat patients with preeclampsia is urgently needed. Ubiquitin-specific protease 14 (USP14) has emerged as a critical regulator in the development of human cancers and neurodegenerative diseases. However, its role in preeclampsia remains elusive.
The expression of USP14 in placental tissues from healthy donors and preeclampsia patients were determined by quantitative reverse transcription PCR assay. The protein levels of targeted genes were evaluated by Western blotting assay. Small interfering RNA-mediated gene knockdown was used to reduce USP14 expression in trophoblast cell lines.
The expression levels of USP14 and proinflammatory cytokine were substantially upregulated in placental tissues from preeclampsia patients. Knockdown or inhibition of USP14 significantly abrogated hypoxia/reoxygenation-induced upregulation of nuclear factor kappa B (NF-κB) activation and proinflammatory cytokine production.
Our results suggested that USP14 promotes proinflammatory cytokine production through activation of NF-κB. Developing drugs targeting USP14 may be beneficial for the prevention or treatment of patients with preeclampsia.
子痫前期可对孕妇和婴儿造成严重后果，因此迫切需要开发有效的药物或方法来预防或治疗子痫前期患者。泛素特异性蛋白酶 14（USP14）已成为人类癌症和神经退行性疾病发展的关键调节因子。然而，其在子痫前期中的作用仍不清楚。
通过定量逆转录 PCR 检测试剂盒检测健康供体和子痫前期患者胎盘组织中 USP14 的表达。通过 Western blot 检测试剂盒评估靶向基因的蛋白水平。使用小干扰 RNA 介导的基因敲低来降低滋养细胞系中 USP14 的表达。
子痫前期患者胎盘组织中 USP14 和促炎细胞因子的表达水平显著上调。USP14 的敲低或抑制显著阻断了缺氧/复氧诱导的核因子 kappa B（NF-κB）激活和促炎细胞因子的产生。
我们的研究结果表明，USP14 通过激活 NF-κB 促进促炎细胞因子的产生。针对 USP14 的药物开发可能有益于子痫前期患者的预防或治疗。
