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微小 RNA let-7c 通过抑制 NF-κB 信号通路改善脂多糖诱导的子宫内膜炎的结局。

MicroRNA let-7c Improves LPS-Induced Outcomes of Endometritis by Suppressing NF-κB Signaling.

机构信息

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.

出版信息

Inflammation. 2019 Apr;42(2):650-657. doi: 10.1007/s10753-018-0922-4.

Abstract

Endometritis is a common inflammatory disease which endangers human and animal reproductive health. MicroRNA (miRNA) let-7c plays an important role in the inflammatory process; however, the regulatory underlying mechanism of let-7c in endometritis is unclear. In this study, we confirmed that let-7c was significantly reduced in LPS-induced mouse endometritis model, and overexpression of let-7c was able to effectively reduce uterine tissue damage caused by lipopolysaccharide (LPS), and then, a LPS-induced bovine endometrial epithelial cell (BEND) line was used to mimic the inflammatory model in vitro. Our data showed that overexpression of let-7c significantly reduced the expression of pro-inflammatory cytokines in BEND cells induced by LPS. Meanwhile, immunofluorescence and western blotting results showed that let-7c significantly inhibited LPS-induced phosphorylation of NF-κB, thereby inhibiting downstream pro-inflammatory cytokine expression. Taken together, our results suggested that let-7c ameliorates LPS-induced endometritis by attenuating the expression of pro-inflammatory cytokines via inhibition of the activation of NF-κB.

摘要

子宫内膜炎是一种危害人类和动物生殖健康的常见炎症性疾病。微小 RNA (miRNA) let-7c 在炎症过程中发挥重要作用;然而,let-7c 在子宫内膜炎中的调控机制尚不清楚。在本研究中,我们证实 let-7c 在 LPS 诱导的小鼠子宫内膜炎模型中显著降低,而过表达 let-7c 能够有效减轻脂多糖(LPS)引起的子宫组织损伤,然后,使用 LPS 诱导的牛子宫内膜上皮细胞(BEND)系在体外模拟炎症模型。我们的数据表明,过表达 let-7c 可显著降低 LPS 诱导的 BEND 细胞中促炎细胞因子的表达。同时,免疫荧光和 Western blot 结果表明,let-7c 显著抑制 LPS 诱导的 NF-κB 磷酸化,从而抑制下游促炎细胞因子的表达。综上所述,我们的研究结果表明,let-7c 通过抑制 NF-κB 的激活来减轻 LPS 诱导的子宫内膜炎,从而减轻促炎细胞因子的表达。

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