Underlying Paracellular Absorption Mechanism of Egg White-Derived Peptide QIGLF: Insight from 4D-FastDIA Proteomic

Paracellular transport is the primary pathway for the intact absorption of the egg white-derived peptide QIGLF. This study aimed to explore the paracellular absorption process of QIGLF in Caco-2 cells using 4D-FastDIA proteomics. A total of 147 differentially expressed proteins (DEPs) were identified. Gene Ontology enrichment analysis revealed that key DEPs, including GRHL2, ECT2, and MARVELD2 involved in apical junction assembly and tight junctions, as well as ARHGEF18 and EphA2 in the plasma membrane, participate in regulating the paracellular absorption of QIGLF. KEGG pathway analysis further indicated that Toll-like receptors and nuclear factor-kappa B-signaling pathways, along with the phosphatidylinositol signaling system, were closely associated with this absorption process. Altogether, the findings of this study demonstrate that QIGLF may alter the expression or subcellular localization of tight junction proteins through these signaling pathways, thereby modulating intestinal tight junction permeability and facilitating its paracellular absorption.