Bovine milk-derived exosomes enhance goblet cell activity and prevent the development of experimental necrotizing enterocolitis

微泡 粘蛋白 杯状细胞 外体 坏死性小肠结肠炎 生物 细胞生物学 粘蛋白2 免疫学 内科学 上皮 医学 小RNA 基因表达 生物化学 遗传学 基因
作者
Bo Li,Alison Hock,Richard Wu,Adam Minich,Steven R. Botts,Carol Lee,Lina Antounians,Hiromu Miyake,Yuhki Koike,Yong Chen,Augusto Zani,Philip M. Sherman,Agostino Pierro
出处
期刊:PLOS ONE [Public Library of Science]
卷期号:14 (1): e0211431-e0211431 被引量:136
标识
DOI:10.1371/journal.pone.0211431
摘要

Necrotizing enterocolitis (NEC) is characterized by intestinal injury and impaired mucin synthesis. We recently showed that breast milk exosomes from rodents promote intestinal cell viability, epithelial proliferation, and stem cell activity, but whether they also affect mucus production is unknown. Therefore, the aim of this study was to investigate the effects of bovine milk-derived exosomes on goblet cell expression in experimental NEC and delineate potential underlying mechanisms of action. Exosomes were isolated from bovine milk by ultracentrifugation and confirmed by Nanoparticle Tracking Analysis and through the detection of exosome membrane markers. To study the effect on mucin production, human colonic LS174T cells were cultured and exposed to exosomes. Compared to control, exosomes promoted goblet cell expression, as demonstrated by increased mucin production and relative expression levels of goblet cell expression markers trefoil factor 3 (TFF3) and mucin 2 (MUC2). In addition, exosome treatment enhanced the expression of glucose-regulated protein 94 (GRP94), the most abundant intraluminal endoplasmic reticulum (ER) chaperone protein that aids in protein synthesis. Furthermore, experimental NEC was induced in mouse pups by hyperosmolar formula feeding, lipopolysaccharide administration and hypoxia exposure on postnatal days 5-9. Milk exosomes were given with each gavage feed. NEC was associated with ileal morphological injury and reduction in MUC2+ goblet cells and GRP94+ cells per villus. Exosome administration to NEC pups prevented these changes. This research highlights the potential novel application of milk-derived exosomes in preventing the development of NEC in high-risk infants when breast milk is not available.
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