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Updated: Nov 10, 2025

Recapitulating Suckling-to-Weaning Transition In Vitro using Fetal Intestinal Organoids
Published on: November 15, 2019
Exosomal circRNAs contribute to intestinal development via the VEGF signalling pathway in human term and preterm
Yahui Zhou1,2, Zhangbin Yu1, Xingyun Wang1
1Department of Pediatrics, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing 210004, China.
Insights
Human breast milk exosomes contain circular RNAs that promote infant intestinal cell growth. These exosomal circular RNAs may regulate the VEGF signaling pathway, impacting infant intestinal development.
Area of Science:
- Neonatal nutrition
- Molecular biology
- Gastroenterology
Background:
- Human breast milk (HBM) is crucial for infant development, containing bioactive molecules like RNAs within exosomes.
- Previous research indicates exosomal circRNAs influence intestinal epithelial cell repair.
- The specific role of HBM exosomal circRNAs in infant intestinal development remains largely unknown.
Purpose of the Study:
- To investigate the impact of human colostrum-derived exosomal circRNAs on infant intestinal development.
- To identify differentially expressed circRNAs in preterm and term colostrum and their potential targets.
- To explore the mechanism by which these circRNAs influence intestinal epithelial cells.
Main Methods:
- Identification and quantification of circRNAs in preterm colostrum (PC) and term colostrum (TC).
- Bioinformatic analysis including pathway and network analysis to identify key signaling pathways and miRNA targets.
- In vitro experiments using exosomes from PC and TC to assess effects on small intestinal epithelial cells (FHCs) and VEGF protein expression.
Main Results:
- 6756 circRNAs were identified in both PC and TC, with 66 upregulated and 42 downregulated in PC.
- Pathway analysis implicated the VEGF signaling pathway, and network analysis revealed interactions between circRNAs and miRNAs.
- Exosomes from PC and TC promoted VEGF protein expression and enhanced FHC proliferation and migration.
Conclusions:
- Human colostrum exosomal circRNAs are differentially expressed and potentially regulate the VEGF signaling pathway.
- These exosomal circRNAs may play a significant role in promoting infant intestinal epithelial cell proliferation and migration.
- Further research into HBM exosomal circRNAs offers insights into infant intestinal development and potential therapeutic strategies.
Abstract:
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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