College of Veterinary Medicine, Northwest A&F University, Yangling, China.
Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, China.
Reprod Domest Anim. 2020 Dec;55(12):1725-1734. doi: 10.1111/rda.13832. Epub 2020 Oct 27.
The endometrium plays an important role in the defence against invading pathogens, although the mechanisms are not clear. UFMylation is a recently discovered novel ubiquitination-like modification system that plays a pivotal role in inflammation and the immune response. The purpose of this study was to investigate the effects of UFMylation on lipopolysaccharide (LPS)-induced inflammatory responses in immortalized goat endometrial epithelial cells (gEECs). Ubiquitin-fold modifier conjugating enzyme 1 (UFM1) and DDRGK domain containing 1 (DDRGK1) were mainly localized in the luminal epithelium and glandular epithelium of mouse and goat endometrial tissues. The expression levels of UFM1, ubiquitin-like modifier activating enzyme 5 (UBA5), UFM1 specific ligase 1 (UFL1) and DDRGK1, as key components of the UFMylation system, were significantly activated by 5 μg/mL LPS-induced inflammatory response in gEECs for 6 hr. Meanwhile, the expression levels of interleukin-6 (IL-6) were significantly upregulated, and tumour necrosis factor-α (TNF-α) was significantly down-regulated after overexpression of UFM1 in gEECs. Additionally, we observed UFM1 and DDRGK1 were markedly increased on LPS-stimulated mouse endometritis in vivo. In conclusion, the current study demonstrated that UFMylation was significantly activated by LPS and might be involved in regulating inflammatory response in gEECs.
子宫内膜在抵御入侵病原体方面起着重要作用,尽管其机制尚不清楚。泛素样修饰(UFMylation)是一种新发现的新型泛素化样修饰系统,在炎症和免疫反应中起着关键作用。本研究旨在探讨 UFMylation 对脂多糖(LPS)诱导的永生化山羊子宫内膜上皮细胞(gEEC)炎症反应的影响。泛素折叠修饰酶 1(UFM1)和 DDRGK 结构域包含蛋白 1(DDRGK1)主要定位于小鼠和山羊子宫内膜组织的腔上皮和腺上皮中。UFMylation 系统的关键组成部分 UFM1、泛素样修饰酶激活酶 5(UBA5)、UFM1 特异性连接酶 1(UFL1)和 DDRGK1 的表达水平在 gEECs 中被 5μg/mL LPS 诱导的炎症反应显著激活 6 小时。同时,在 gEECs 中转染 UFM1 后,白细胞介素 6(IL-6)的表达水平显著上调,肿瘤坏死因子-α(TNF-α)的表达水平显著下调。此外,我们观察到 LPS 刺激的体内小鼠子宫内膜炎中 UFM1 和 DDRGK1 的表达明显增加。综上所述,本研究表明 LPS 可显著激活 UFMylation,并可能参与调节 gEECs 的炎症反应。