The Potential Therapeutic Role of miR-223 in Bovine Endometritis by Targeting the NLRP3 Inflammasome.

The Potential Therapeutic Role of miR-223 in Bovine Endometritis by Targeting the NLRP3 Inflammasome.
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miR-223 通过靶向 NLRP3 炎症小体在牛子宫内膜炎中的潜在治疗作用

DOI:
10.3389/fimmu.2018.01916
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发表时间:
2018
影响因子:
7.3
通讯作者:
Deng G
Deng G
中科院分区:
医学2区
文献类型:
--
作者:
Zhao G;Jiang K;Yang Y;Zhang T;Wu H;Shaukat A;Qiu C;Deng G

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牛子宫内膜炎影响奶牛的产奶量和繁殖性能,造成严重的经济损失。牛子宫内膜炎的潜在分子机制或信号通路仍不清楚。在本研究中,我们试图确定mir-223在奶牛子宫内膜炎中的表达机制并评估其潜在的治疗价值。我们首先证实子宫内膜炎中 miR-223 水平升高,然后使用 LPS 诱导的牛子宫内膜上皮细胞 (BEND) 系来模拟体外炎症模型。我们的数据表明,NF-κB 的激活促进 miR-223 的转录,从而抑制炎症介质 NLRP3 的激活及其介导的 IL-1β 产生,从而防止炎症损伤。同时,体内研究表明,抑制 mir-223 会导致 LPS 诱导的子宫内膜炎期间小鼠的病理学增强,而 mir-223 的过度表达会减轻子宫内的炎症状况。总之,我们的研究强调,miR-223 既可以限制 NLRP3 的激活水平,又可以作为炎症反应中的保护因子,从而为奶牛子宫内膜炎和其他炎症性疾病的活跃发作提供一种未来的新型治疗方式。
Bovine endometritis affects milk production and reproductive performance in dairy cows and causes serious economic loss. The underlying molecular mechanisms or signaling pathways of bovine endometritis remain unclear. In this study, we attempted to determine the expression mechanism of mir-223 in endometritis of dairy cows and evaluate its potential therapeutic value. We first confirmed that there was an increased level of miR-223 in endometritis, and then, an LPS-induced bovine endometrial epithelial cell (BEND) line was used to mimic the inflammatory model in vitro. Our data showed that activation of NF-κB promoted the transcription of miR-223, thus inhibiting activation of the inflammatory mediator NLRP3 and its mediation of IL-1β production to protect against inflammatory damage. Meanwhile, in vivo studies showed that inhibition of mir-223 resulted in an enhanced pathology of mice during LPS-induced endometritis, while overexpression of mir-223 attenuated the inflammatory conditions in the uterus. In summary, our study highlights that miR-223 serves both to constrain the level of NLRP3 activation and to act as a protective factor in the inflammatory response and thus provides a future novel therapeutic modality for active flares in cow endometritis and other inflammatory diseases.
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