MiR-125b regulates inflammation in bovine mammary epithelial cells by targeting the NKIRAS2 gene.
MiR-125b regulates inflammation in bovine mammary epithelial cells by targeting the NKIRAS2 gene.
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DOI：
10.1186/s13567-021-00992-0
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发表时间：
2021-09-17
影响因子：
4.4
通讯作者：
Wang XP
中科院分区：
文献类型：
--
作者：
Luoreng ZM;Wei DW;Wang XP
乳房炎是奶牛乳房组织因病原性感染而引起的一种复杂的炎症性疾病。其发生、发展和调控的分子机制由包括microRNA（miRNA）在内的多基因网络组成。到目前为止，还没有关于miR-125 b在调节奶牛乳房炎中的作用的报道。本研究发现，在脂多糖（LPS）诱导的MAC-T牛乳腺上皮细胞中，miR-125 b的表达显著降低。其表达与NF-κB抑制剂相互作用Ras样2（NKIRAS 2）基因表达呈负相关。利用双荧光素酶报告基因分析法鉴定miR-125 b靶基因，结果显示miR-125 b可与NKIRAS 2的3′非翻译区（3′ UTR）结合，但不能与TNF-α诱导蛋白3（TNFAIP 3）的3′UTR结合。此外，使用miR-125 b过表达和沉默来研究miR-125 b在LPS诱导的MAC-T中对炎症的作用。结果表明，LPS诱导的MAC-T细胞中miR-125 B表达的降低增加了NKIRAS 2表达，其随后降低了NF-κB活性，导致炎性因子IL-6和TNF-α的低表达。最终，这减少了MAC-T细胞中的炎症反应。这些结果表明，miR-125 b是一种促炎调节因子，其沉默可以减轻牛乳腺炎。这些结果为阐明奶牛乳房炎的分子调控机制奠定了基础。在线版本包含补充材料，可通过10.1186/s13567-021-00992-0获得。
Mastitis is a complex inflammatory disease caused by pathogenic infection of mammary tissue in dairy cows. The molecular mechanism behind its occurrence, development, and regulation consists of a multi-gene network including microRNA (miRNA). Until now, there is no report on the role of miR-125b in regulating mastitis in dairy cows. This study found that miR-125b expression is significantly decreased in lipopolysaccharide (LPS)-induced MAC-T bovine mammary epithelial cells. Also, its expression is negatively correlated with the expression of NF-κB inhibitor interacting Ras-like 2 (NKIRAS2) gene. MiR-125b target genes were identified using a double luciferase reporter gene assay, which showed that miR-125b can bind to the 3′ untranslated region (3′ UTR) of the NKIRAS2, but not the 3′UTR of the TNF-α induced protein 3 (TNFAIP3). In addition, miR-125b overexpression and silencing were used to investigate the role of miR-125b on inflammation in LPS-induced MAC-T. The results demonstrate that a reduction in miR-125b expression in LPS-induced MAC-T cells increases NKIRAS2 expression, which then reduces NF-κB activity, leading to low expression of the inflammatory factors IL-6 and TNF-α. Ultimately, this reduces the inflammatory response in MAC-T cells. These results indicate that miR-125b is a pro-inflammatory regulator and that its silencing can alleviate bovine mastitis. These findings lay a foundation for elucidating the molecular regulation mechanism of cow mastitis. The online version contains supplementary material available at 10.1186/s13567-021-00992-0.
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