Zhang Chao, Zheng Jie, Han Xueting, Zhao Jingwen, Cheng Shihui, Li Aili
State Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Company Limited, Shanghai 200436, China.
Key Laboratory of Dairy Science, Ministry of Education, College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, China.
J Agric Food Chem. 2024 Apr 12. doi: 10.1021/acs.jafc.3c09856.
Inflammatory bowel disease (IBD) is a common disease of the digestive system, and an excessive immune response mediated by the nuclear factor κ-B (NF-κB) signaling pathway is an essential etiology. Recent studies have found that bovine milk exosomes can improve intestinal mucosal health by delivering microRNA (miRNA), but the mechanism of action is so far unknown. In the present study, we analyzed the differential expression profiles of miRNA in colostrum and mature milk exosomes using high-throughput sequencing, based on the demonstration that colostrum exosomes inhibit the lipopolysaccharide (LPS)-induced intestinal epithelial NF-κB inflammatory pathway better than mature milk exosomes. The bta-miR-30a-5p, which is specifically highly expressed in colostrum, was screened, and its predicted target gene TRAM was found to be closely related to the NF-κB signaling pathway by functional enrichment analysis. Further, we used gene overexpression and silencing techniques and found that the bta-miR-30a-5p transfection treatment was confirmed to inhibit LPS-induced NF-κB signaling pathway activation and downstream pro-inflammatory factor expression, while the expression of its potential target gene, TRAM, was also suppressed. It is hypothesized that the high expression of bta-miR-30a-5p in colostrum, which targets TRAM to inhibit the downstream NF-κB inflammatory pathway, may be one of the molecular mechanisms responsible for its superior effect on resisting inflammatory attack compared to mature milk.
炎症性肠病（IBD）是一种常见的消化系统疾病，由核因子κ-B（NF-κB）信号通路介导的过度免疫反应是其重要病因。最近的研究发现，牛乳外泌体可通过递送微小RNA（miRNA）改善肠道黏膜健康，但其作用机制尚不清楚。在本研究中，基于初乳外泌体比成熟乳外泌体更能抑制脂多糖（LPS）诱导的肠上皮NF-κB炎症通路这一证据，我们利用高通量测序分析了初乳和成熟乳外泌体中miRNA的差异表达谱。筛选出在初乳中特异性高表达的bta-miR-30a-5p，并通过功能富集分析发现其预测靶基因TRAM与NF-κB信号通路密切相关。此外，我们使用基因过表达和沉默技术，发现bta-miR-30a-5p转染处理可抑制LPS诱导的NF-κB信号通路激活及下游促炎因子表达，同时其潜在靶基因TRAM的表达也受到抑制。据推测，初乳中bta-miR-30a-5p的高表达通过靶向TRAM抑制下游NF-κB炎症通路，可能是其比成熟乳更能有效抵抗炎症攻击的分子机制之一。
