Porcine milk-derived exosomes promote proliferation of intestinal epithelial cells

Abstract

Milk-derived exosomes were identified as a novel mechanism of mother-to-child transmission of regulatory molecules, but their functions in intestinal tissues of neonates are not well-studied. Here, we characterized potential roles of porcine milk-derived exosomes in the intestinal tract. In vitro, treatment with milk-derived exosomes (27 ± 3 ng and 55 ± 5 ng total RNA) significantly promoted IPEC-J2 cell proliferation by MTT, CCK8, EdU fluorescence and EdU flow cytometry assays. The qRT-PCR and Western blot analyses indicated milk-derived exosomes (0.27 ± 0.03 μg total RNA) significantly promoted expression of CDX2, IGF-1R and PCNA, and inhibited p53 gene expression involved in intestinal proliferation. Additionally, six detected miRNAs were significantly increased in IPEC-J2 cell, while FAS and SERPINE were significantly down-regulated relative to that in control. In vivo, treated groups (0.125 μg and 0.25 μg total RNA) significantly raised mice’ villus height, crypt depth and ratio of villus length to crypt depth of intestinal tissues, significantly increased CDX2, PCNA and IGF-1R’ expression and significantly inhibited p53′ expression. Our study demonstrated that milk-derived exosomes can facilitate intestinal cell proliferation and intestinal tract development, thus giving a new insight for milk nutrition and newborn development and health.

Characterization and biological function of milk‐derived miRNAs

“…Some miRNAs that exist in milk may be involved in various physiological functions including regulation of cell growth and differentiation , and could influence the development and maturation of the infants gut and other organs. There are experimental proof that milk exosomes are taken up by intestinal epithelial cells and promote intestinal cell growth and proliferation of intestinal epithelial cells . In addition, we found that miRNA‐148a is highly expressed in human milk.…”

Colostrum Management for Dairy Calves

“…MiRNAs are short, noncoding RNA molecules that can regulate gene expression at the posttranscriptional level, and could represent one possible method of postnatal signaling from the mother to the neonate. Although studies are needed to describe their functional significance in calves, early research in other species suggests that, once absorbed by the neonate, MiRNAs from colostrum may be important in the differentiation and functional development of the intestinal epithelium, 44 and could also play an important role in the maturation of the neonate's immune system. 45 These nutrients and nonnutritive factors, combined with benefits of disease protection from Ig, may contribute to the short-term and long-term benefits from improved colostrum intake, including improved rate of gain, reduced age at first calving, improved first and second lactation milk production, and reduced tendency for culling during the first lactation.…”

Milk MicroRNAs in Health and Disease

“…Functionality of milk EVs has been explored following their intrinsic biological activity or their potential as drug carriers for cancer treatment (Agrawal et al., ; Aqil et al., , ; Badawy et al., ; Munagala et al., , ; Qin et al., ; Somiya et al., ), for the modulation of inflammation (Admyre et al., ; Arntz et al., ; Badawy et al., ; Martin et al., ; Vashisht et al., ), for gut, bone, and muscle development (Chen et al., ; Hock et al., ; Leiferman et al., ; Martin et al., ; Mobley et al., ; Oliveira et al., , ), bacterial proliferation (Yu et al., ), and in the prevention of HIV infection (Naslund et al., ).…”

“…Finally, milk EVs have been implicated in vitro and in vivo in bone growth and bone degradation (Oliveira et al., ; Oliveira et al., ), promotion of gut development (Chen et al., ; Martin et al., ), attenuation of intestinal cell death (Martin et al., ), and muscle growth, with whey EVs (Mobley et al., ), being more potent than milk EVs (Leiferman et al., ) to promote muscle development.…”