Immunoglobulin-derived peptide MEANP1 of human Milk in the protection against experimental necrotizing Enterocolitis via IκB/ NF-κB pathway

Abstract

Necrotizing enterocolitis (NEC) is one of the most common intestinal emergencies in newborn infants. It is closely related to abnormal activation of intestinal inflammation and impaired barrier function. Studies have shown that breast milk exosomes can effectively improve NEC, but the specific mechanism remains unclear. Human breast milk exosomal cargoes are emerging as new modulators for NEC. To evaluate the function and potential mechanisms of action of peptide MEANP1 both in vivo and in vitro. MEANP1 was found to improve the survival rate, abdominal distension and hematochezia in NEC models. Intestinal histological damage was improved, along with decreased expression of pro-inflammatory factors and increased expression of intestinal barrier protein. In IEC-6 cells, MEANP1 can improve LPS-induced inhibition of proliferation, migration and barrier damage. The pro-inflammatory factors TLR4, TNF-α and IL-1β were inhibited by MEANP1. We verified by RNA-seq technique and rescue experiment that it can inhibit the phosphorylation of NF-κB by inhibiting the phosphorylation of IκBα to protect from NEC. MEANP1 is expected to be a treatment for NEC.

Keywords

• Necrotizing enterocolitis
• Peptide
• NF-κB
• Intestinal barrier function
• IκB