文献类型：期刊文献

英文题名：Bta-miR-223 Targeting CBLB Contributes to Resistance toStaphylococcus aureusMastitis Through the PI3K/AKT/NF-κB Pathway

作者：Han, Shuo[1];Li, Xinli[1];Liu, Juan[1];Zou, Ziwen[1];Luo, Lin[1];Wu, Rui[1,2];Zhao, Zhihui[3];Wang, Changyuan[1];Shen, Binglei[1,2,4]

机构：[1]Heilongjiang Bayi Agr Univ, Coll Anim Sci & Vet Med, Daqing, Peoples R China;[2]Heilongjiang Bayi Agr Univ, Heilongjiang Prov Key Lab Prevent & Control Bovin, Daqing, Peoples R China;[3]Guangdong Ocean Univ, Agr Coll, Zhanjiang, Peoples R China;[4]Heilongjiang Bayi Agr Univ, Heilongjiang Prov Key Lab Efficient Utilizat Feed, Daqing, Peoples R China

年份：2020

卷号：7

外文期刊名：FRONTIERS IN VETERINARY SCIENCE

收录：SCI-EXPANDED(收录号：WOS:000570174700001)、、WOS

基金：This work was supported by National Natural Science Foundation of China, grant numbers 31472249, 31772562, and 31200922; National Major Special Project on New Varieties Cultivation for Transgenis Organisms, grant number 2016ZX08009003-006; China Postdoctoral Science Foundation Project, grant number 2018M631970; Heilongjiang Province Postdoctoral Startup Fund Project, grant number LBH-Z16166; Heilongjiang Provincial Department of Education Science and Technology Research Project, grant number 12521365; Heilongjiang Bayi Agricultural University Youth Innovation Talent Project, grant number CXRC-2016-06; Heilongjiang Bayi Agricultural University Postdoctoral Startup Fund Project, grant number XDB-2017-06; and Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases, grant number PCBD201708. Funders only provide fund support in this study, and have no role in designing research, collecting, analyzing, interpreting data, writing manuscripts, and other events.

语种：英文

外文关键词：Staphylococcus aureus; bovine mastitis; bta-miR-223; CBLB; resistance regulation mechanism

外文摘要：Bovine mastitis is an inflammatory condition of the mammary gland often caused by (Staphylococcus aureus)S. aureusinfection. The aim of this study was to identify mastitis-related miRNAs and their downstream target genes, and therefore elucidate the regulatory mechanisms involved in disease progression and resistance. Three healthy and three mastitic cows were identified on the basis of the somatic cell count and bacterial culture of their milk, and the histological examination of udder tissues. High-throughput RNA sequencing and bioinformatic analyses revealed that 48 differentially expressed miRNAs (DEMs) in the mastitic udder tissues relative to the healthy tissues. Among 48 DEMs, the expression level of bta-miR-223 was the most up-regulated. Overexpression of the bta-miR-223 in Mac-T cells mitigated the inflammatory pathways induced byS. aureus-derived lipoteichoic acid (LTA). The Cbl proto-oncogene B (CBLB) was identified as the target gene of bta-miR-223, and the direct binding of the miRNA to the CBLB promoter was confirmed by dual luciferase reporter assay using wild-type and mutant 3'-UTR constructs. Furthermore, overexpression ofCBLBin the LTA-stimulated Mac-T cells significantly upregulated PI3K, AKT, and phosphorylated NF-kappa B p65, whereasCBLBknockdown had the opposite effect. Consistent with thein vitrofindings, the mammary glands of mice infected with 10(8)CFU/100 mu LS. aureusshowed high levels of CBLB, PI3K, AKT, and p-NF-kappa B p65 48 h after infection. Taken together, bta-miR-223 is a predominant miRNA involved in mastitis, and bta-miR-223 likely mitigates the inflammatory progression by targeting CBLB and inhibiting the downstream PI3K/AKT/NF-kappa B pathway.