Protective Effects of Milk-Derived Extracellular Vesicles on Colitic Mice via ceRNA Network Involving lncRNAs and circRNAs

Our previous work demonstrated that bovine milk-derived extracellular vesicles (mEVs) could alleviate the inflammatory response of mice colitis, along with hundreds of differentially expressed (DE) mRNAs. This study further analyzed the profiles of non-coding RNAs (ncRNAs) and explored the correlation with DE mRNAs by constructing ceRNA networks. Six-week-old male C57BL/6 mice were fed either a control diet or a diet added with mEVs for 30 days. Then the mice were given dextran sulphate sodium in drinking water for 7 days to induce colitis. A total of 40 miRNAs, 541 lncRNAs and 643 circRNAs exhibited changes in mEVs pretreatment group. Among these DE miRNAs, mEVs pretreatment significantly increased the expressions of miR-122, miR-147, miR-210, miR-1224, miR-148a, and miR-212, which might participate in the inflammatory response of the colitis models. The expression of Tug1 increased after mEVs pretreatment, while Snhg5 and H19 decreased, which might be involved in intestinal barrier restoration. Functional analysis of the DE ncRNAs suggested mEVs might exert protective effects not only through modulation of inflammatory responses but also by enhancing intestinal stem cell function and epithelial regeneration, which were mainly regulated by Wnt and Hippo signaling pathways according to the ceRNA networks.