畜牧与饲料科学 ›› 2025, Vol. 46 ›› Issue (3): 9-16.doi: 10.12160/j.issn.1672-5190.2025.03.002

• 基础研究 • 上一篇    下一篇

基于MAPK信号通路探讨牛乳及其外泌体关键miRNA的免疫调节机制

王乐乐1, 王高峰2, 赵濛3   

  1. 1.乌兰察布医学高等专科学校,内蒙古 集宁 012000;
    2.乌兰察布市动物疫病预防控制中心,内蒙古 集宁 012000;
    3.内蒙古自治区农牧业科学院,内蒙古 呼和浩特 010031
  • 收稿日期:2025-03-14 出版日期:2025-05-30 发布日期:2025-09-02
  • 通讯作者: 赵濛(1988—),男,助理研究员,博士,主要研究方向为反刍动物营养调控与基因调控互作及调控剂研发。
  • 作者简介:王乐乐(1985—),女,副教授,博士,主要研究方向为分子遗传学。
  • 基金资助:
    内蒙古自然科学基金项目(2025LHMS03065,2020LH03021);乌兰察布医学高等专科学校校级科研项目(WLCBYZK202302)

Exploring the Immunomodulatory Mechanisms of Key miRNAs in Bovine Milk and Milk-derived Exosomes via the MAPK Signaling Pathway

WANG Lele1, WANG Gaofeng2, ZHAO Meng3   

  1. 1. Wulanchabu Medical College, Jining 012000, China;
    2. Ulanqab Animal Disease Dreventim and Control Center, Jining 012000, China;
    3. Inner Mongolia Academy of Agricultural and Animal Husbandry Sciences, Hohhot 010031, China
  • Received:2025-03-14 Online:2025-05-30 Published:2025-09-02

摘要: [目的]解析牛乳及其外泌体MAPK通路miRNA的免疫调节机制。[方法]结合前期测序数据,筛选牛乳及牛乳外泌体中MAPK信号通路免疫关键miRNA,再使用TargetScan和miRanda软件对筛选出的免疫关键miRNA进行靶基因预测和靶基因生物信息学功能分析,最后构建免疫关键miRNA的miRNA-mRNA-KEGG调节网络。[结果]牛乳及其外泌体MAPK通路免疫相关关键miRNA有80个,靶基因在regulation of inflammatory response(GO:0050727,炎症反应的调控)和negative regulation of inflammatory response(GO:0050728,炎症反应的负向调控)等免疫相关的GO Term上显著富集。靶基因共富集在335个KEGG通路中,其中富集基因数目位居前5的KEGG通路是Metabolism(新陈代谢)、MAPK(丝裂原活化蛋白激酶通路)、Pathways in cancer(癌症相关通路)、Endocytosis(内吞作用)和Carbon metabolism(碳代谢)。调控网络中的基因PDGFRAPDGFRB通过MAPK信号通路的多个miRNA介导牛乳及其外泌体的免疫功能。[结论]MAPK信号通路通过bta-let-7i、bta-miR-155、bta-miR-34a、bta-miR-499b和bta-miR-106a_R+1_1ssIAC等关键miRNA 介导牛乳及其外泌体免疫抗性。调控网络中的基因PDGFRAPDGFRB受到MAPK信号通路的多个miRNA的调控,可能是牛乳及其外泌体免疫调控的关键基因。

关键词: 牛乳外泌体, MAPK, miRNA, 免疫调控

Abstract: [Objective] To analyze the immunomodulatory mechanism of miRNA in the MAPK signaling pathway of bovine milk and milk-derived exosomes. [Methods] Key immune miRNAs of MAPK signaling pathway in bovine milk and milk-derived exosomes were screened based on previous sequencing data. Target genes of these miRNAs were predicted using TargetScan and miRanda software, and their bioinformatics functions were analyzed. Finally, the miRNA-mRNA-KEGG regulatory network of immune-related key miRNAs was constructed. [Results] There were 80 key miRNAs in bovine milk and milk-derived exosomes. The target genes were significantly enriched in immune-related GO terms, including "regulation of inflammatory response" (GO:0050727) and "negative regulation of inflammatory response" (GO:0050728). KEGG pathway analysis revealed enrichment in 335 pathways, with the top five being "Metabolism", "MAPK signaling pathway", "Pathways in cancer", "Endocytosis" and "Carbon metabolism". PDGFRA and PDGFRB genes in the regulatory network mediated immune functions of bovine milk and milk-derived exosomes through MAPK signaling pathway-associated miRNAs. [Conclusion] MAPK signaling pathway mediated the immune resistance in bovine milk and milk-derived exosomes via key miRNAs, such as bta-let-7i, bta-miR-155, bta-miR-34a, bta-miR-499b and bta-miR-106a_R+1_1ssIAC. PDGFRA and PDGFRB genes in the regulatory network regulated by multiple MAPK signaling pathway-associated miRNAs, might be the key genes in the immune regulation of bovine milk and milk-derived exosomes.

Key words: milk-derived exosomes, MAPK, miRNA, immune regulation

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