Exosomal circRNAs contribute to intestinal development via the VEGF signalling pathway in human term and preterm colostrum.
Exosomal circRNAs contribute to intestinal development via the VEGF signalling pathway in human term and preterm colostrum.
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外泌体 circRNA 通过人类足月和早产初乳中的 VEGF 信号通路促进肠道发育
DOI：
10.18632/aging.202806
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发表时间：
2021-04-04
期刊：
影响因子：
--
通讯作者：
Han S
中科院分区：
文献类型：
--
作者：
Zhou Y;Yu Z;Wang X;Chen W;Liu Y;Zhang Y;Yin J;Han S
人母乳（HBM）为新生儿的生长发育提供必需的营养物质，并且包含多种生物活性成分，这些成分会影响母乳喂养婴儿的胃肠道和免疫系统发育。人母乳还含有信使核糖核酸（mRNAs）、微小核糖核酸（microRNAs）和长链非编码核糖核酸（lncRNAs），其中大部分被包裹在母乳来源的外泌体中，并展现出各种与婴儿发育相关的重要生物学功能。虽然先前的研究表明外泌体环状核糖核酸（circRNAs）参与肠道上皮细胞的增殖和修复，但是人母乳外泌体环状核糖核酸对肠道发育的影响尚不明确。在本研究中，我们在早产初乳（PC）和足月产初乳（TC）中均鉴定出6756种环状核糖核酸，其中在早产初乳中有66种上调，42种下调（|倍数变化>2|，p < 0.05）。通路分析表明血管内皮生长因子（VEGF）信号通路参与其中，网络分析显示差异表达的环状核糖核酸与多种微小核糖核酸结合。进一步分析表明has_circRNA_405708和has_circRNA_104707参与血管内皮生长因子信号通路，并且它们都与多种微小核糖核酸结合。在早产初乳和足月产初乳中发现的外泌体促进血管内皮生长因子蛋白表达，并诱导小肠上皮细胞（FHCs）的增殖和迁移。在人初乳中发现的外泌体环状核糖核酸与相关微小核糖核酸结合可能调节血管内皮生长因子信号通路以及肠道发育。
Human breast milk (HBM) provides essential nutrients for newborn growth and development, and contains a variety of biologically active ingredients that can affect gastrointestinal tract and immune system development in breastfed infants. HBM also contains mRNAs, microRNAs and lncRNAs, most of which are encapsulated in milk-derived exosomes and exhibit various important infant development related biological functions. While previous studies have shown that exosomal circRNAs are involved in the intestinal epithelial cells’ proliferation and repair. However, the effect of HBM exosomal circRNAs on intestinal development is not clear. In this study, we identified 6756 circRNAs both in preterm colostrum (PC) and term colostrum (TC), of which 66 were upregulated, and 42 were downregulated (|fold change>2|, p < 0.05) in PC. Pathway analysis showed that the VEGF signalling pathway was involved, and network analysis revealed that the differentially expressed circRNAs bound various miRNAs. Further analyses showed that has_circRNA_405708 and has_circRNA_104707 were involved in the VEGF signalling pathway, and that they all bound various mirRNAs. Exosomes found in preterm colostrum (PC) and term colostrum (TC) promoted VEGF protein expression and induced the proliferation and migration of small intestinal epithelial cells (FHCs). Exosomal circRNAs found in human colostrum (HC) binding to related miRNAs may regulate VEGF signalling, and intestinal development.
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