ArticleJournal of animal science and biotechnology2025
Circ-0000197 derived from porcine milk small extracellular vesicles promotes intestinal barrier function by sponging miR-429.
Article in Journal of animal science and biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundAs an essential source of nutrients for young mammals, milk possesses a variety of biological functions. Recently identified milk-derived small extracellular vesicles (sEV) have shown potential regulatory effects on intestinal health. Current studies have highlighted the functional roles of milk-derived sEV and their RNA cargo in promoting intestinal health. However, there is a paucity of research demonstrating how milk-derived sEV influence intestinal barrier function through the transport of circRNAs.
resultsIn this study, we aimed to investigate the effects of porcine milk sEV (PM-sEV) circRNA on intestinal barrier function. We systematically identified the circRNAs involved in this process and analyzed the miRNAs through which PM-sEV deliver circRNAs to regulate intestinal barrier function. Our findings revealed that PM-sEV promote the expression of the intestinal tight junction proteins ZO-1 and Occludin, both in vivo (mice) and in vitro (IPEC-J2). When PM-sEV RNA was reduced using ultrasound treatment, their ability to enhance intestinal barrier function was significantly reduced. Bioinformatics analysis showed that circ-0000197, present in PM-sEV, can target miR-429, while miR-429 has the ability to target the 3'-UTR of ZO-1 and Occludin. Furthermore, experiments involving the overexpression or inhibition of the relevant non-coding RNAs (ncRNAs) demonstrated that circ-0000197 significantly enhances intestinal barrier function, whereas miR-429 exerts an inhibitory effect on this function. Overall, our findings identify circ-0000197 in PM-sEV as a crucial circRNA that regulates intestinal barrier function by inhibiting miR-429. Circ-0000197 carried by PM-sEV acts as a competing endogenous RNA (ceRNA) that regulates the expression of ZO-1 and Occludin by sponging miR-429, thereby promoting intestinal barrier function at both the cellular and in vivo levels.
conclusionsThese findings emphasize the vital role of circRNAs transported through milk-derived sEV in regulating intestinal health, offering new avenues for developing innovative functional milk components. This mechanism also underscores the importance of PM-sEV carrying circ-0000197 in preserving intestinal barrier integrity. Collectively, this study enhances our understanding of the complex regulatory networks involving PM-sEV carrying circRNAs and their impact on intestinal health.
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