Human milk exosomal-miR-144-5p alleviates neonatal necrotizing enterocolitis by regulating the TLR4/NF-κB pathway

Area of Science:

• Neonatal research
• Gastroenterology
• Molecular biology

Background:

• Necrotizing enterocolitis (NEC) is a severe intestinal disease in premature infants.
• Human breast milk exosomes show potential in preventing NEC, but the mechanisms are not fully understood.
• This study investigates the role of miR-144-5p in protecting the intestinal barrier during NEC.

Purpose of the Study:

• To elucidate the mechanism by which exosomal miR-144-5p repairs tight junction barrier damage in NEC.
• To examine the role of miR-144-5p in regulating intestinal inflammation and epithelial barrier integrity.

Main Methods:

• MiRNA sequencing to identify differentially expressed exosomal miRNAs in term and preterm breast milk.
• In vitro and in vivo experiments to study the biological role and mechanism of miR-144-5p.
• Analysis of intestinal epithelial cell viability, claudin-1 and IL-1β protein levels, TLR4 expression, and NF-κB signaling pathway activation.

Main Results:

• Exosomal miR-144-5p enhanced intestinal epithelial cell viability and increased claudin-1 levels.
• Overexpression of miR-144-5p reduced interleukin-1β (IL-1β) levels.
• miR-144-5p alleviated intestinal inflammation by downregulating toll-like receptor 4 (TLR4) and inhibiting the NF-κB pathway.

Conclusions:

• Exosomal miR-144-5p protects against experimental NEC by inhibiting the TLR4/NF-κB signaling pathway.
• This microRNA repairs tight junctions and reduces inflammation, offering a novel therapeutic target for NEC.
• The findings reveal a new regulatory mechanism in NEC pathogenesis and expand therapeutic options.