Paracellular diffusion mechanism of the egg white-derived peptide RVPSL mediated by tight junction-related protein

This study investigated the paracellular diffusion of egg white-derived antihypertensive peptide RVPSL using a 4-dimensional data-independent acquisition-based (4D-DIA) proteomics approach. The 775 differentially expressed proteins were identified after RVPSL transport. Gene Ontology enrichment analysis indicated that 5 key proteins (claudin-1 (CLDN1), epithelialcell-transforming sequence2 (ECT2), epidermal growth factor receptor (EGFR), synaptopodin (SYNPO), α-actinin-4 (ACTN4)) associated with bicellular tight junction assembly, actin filament binding, and actin binding may affect the paracellular diffusion of RVPSL. The egg white-derived peptide RVPSL may trigger the opening of tight junctions by down-regulating the expression of CLDN1 and ECT2 proteins, up-regulating the EGFR protein expression, and may promote the restoration of tight junctions by up-regulating the expression of SYNPO and ACTN4 proteins, thereby enabling paracellular diffusion. Furthermore, the retrograde endocannabinoid signaling pathway may regulate the paracellular diffusion of egg white-derived peptide RVPSL by affecting the expression of tight junction-related proteins. The study provides new ideas and insights to understand the intestinal absorption of egg white-derived peptides to enhance the health-promoting effect.