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microRNA-196b 通过靶向 NRAS 缓解脂多糖诱导的炎症损伤。

microRNA-196b alleviates lipopolysaccharide-induced inflammatory injury by targeting NRAS.

机构信息

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

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

出版信息

Mol Immunol. 2022 Jul;147:10-20. doi: 10.1016/j.molimm.2022.03.122. Epub 2022 Apr 27.

Abstract

Bovine endometritis is a serious hazard to husbandry, so it is necessary to know the mechanism of endometritis. In past research, we found microRNAs (miRNAs) might be regulators in inflammation, including miR-196b, but the mechanism of miR-196b in bovine endometritis was unknown. Therefore, we tended to find out what role miR-196b would play in bovine endometritis. As a result, we found miR-196b up-regulated in the endometritis tissue and the high concentration lipopolysaccharide (LPS)-stimulated bovine endometrial epithelial (BEND) cell line, but down-regulated in the low concentration. And, over-expression of miR-196b inhibited the expressions of some inflammatory factors, such as tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and neuroblastoma RAS (NRAS)/nuclear factor (NF)-κB pathway proteins. Furthermore, the dual-luciferase reporter assay and NRAS knockdown confirmed that miR-196b inhibited activation of the downstream pathway by directly targeting NRAS. In conclusion, we provide evidence that miR-196b alleviates LPS-induced inflammatory injury by targeting NRAS.

摘要

牛子宫内膜炎是畜牧业的严重危害,因此有必要了解子宫内膜炎的发病机制。在过去的研究中,我们发现 microRNAs (miRNAs) 可能是炎症的调节因子,包括 miR-196b,但 miR-196b 在牛子宫内膜炎中的作用机制尚不清楚。因此,我们试图找出 miR-196b 在牛子宫内膜炎中会发挥什么作用。结果发现,miR-196b 在子宫内膜炎组织和高浓度脂多糖(LPS)刺激的牛子宫内膜上皮(BEND)细胞系中上调,但在低浓度时下调。并且,miR-196b 的过表达抑制了一些炎症因子的表达,如肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和神经母细胞瘤 RAS(NRAS)/核因子(NF)-κB 通路蛋白。此外,双荧光素酶报告基因检测和 NRAS 敲低证实,miR-196b 通过直接靶向 NRAS 抑制下游通路的激活。总之,我们提供的证据表明,miR-196b 通过靶向 NRAS 减轻 LPS 诱导的炎症损伤。

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