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miR-495-3p 通过抑制 NLRP3 炎性小体的激活来减轻牛的细胞焦亡和子宫内膜炎。

MiR-495-3p attenuates cell pyroptosis and endometritis through inhibiting the activation of NLRP3 inflammasome in bovine.

机构信息

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

出版信息

Mol Immunol. 2023 Nov;163:75-85. doi: 10.1016/j.molimm.2023.09.007. Epub 2023 Sep 23.

Abstract

miR-495 is aberrantly expressed and affects the progression of inflammation in various diseases. However, the mechanisms of miR-495 in bovine endometritis remain largely unknown. This study investigated the mechanism of miR-495 in lipopolysaccharide (LPS)-induced bovine endometritis and pyroptosis and found that miR-495 inhibits NLRP3 inflammasome activation and inflammatory immune responses in endometritis tissue and cell models. Bovine endometrial epithelial cells (BENDs) were treated with 10 μg/mL LPS to establish a cell inflammatory model. LPS stimulation activated the NLRP3 inflammasome and elevated the expression of proinflammatory factors in BEND cells. In addition, pyroptosis and methylation-dependent inhibition of miR-495 was discovered in LPS-exposed BENDs. Furthermore, overexpression of miR-495 inhibited activation of the NLRP3 inflammasome in vitro and vivo. Collectively, our data demonstrate that miR-495 can attenuate activation of the NLRP3 inflammasome to protect against pyroptosis and bovine endometritis, which provides novel therapeutic targets for bovine endometritis and other inflammatory diseases.

摘要

miR-495 表达异常,影响多种疾病的炎症进展。然而,miR-495 在牛子宫内膜炎中的作用机制在很大程度上尚不清楚。本研究探讨了 miR-495 在脂多糖(LPS)诱导的牛子宫内膜炎和细胞焦亡中的作用机制,发现 miR-495 抑制子宫内膜炎组织和细胞模型中 NLRP3 炎性小体的激活和炎症免疫反应。用 10μg/mL LPS 处理牛子宫内膜上皮细胞(BEND)建立细胞炎症模型。LPS 刺激激活 NLRP3 炎性小体,增加 BEND 细胞中促炎因子的表达。此外,在 LPS 暴露的 BEND 中发现了焦亡和 miR-495 的甲基化依赖性抑制。此外,miR-495 的过表达抑制了体外和体内 NLRP3 炎性小体的激活。综上所述,我们的数据表明,miR-495 可以减轻 NLRP3 炎性小体的激活,从而防止细胞焦亡和牛子宫内膜炎,为牛子宫内膜炎和其他炎症性疾病提供了新的治疗靶点。

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