GOLM1 interacts with EGFR and contributes to increased intestinal permeability in ulcerative colitis through p38 MAPK signaling

Golgi membrane protein 1 (GOLM1) has been implicated in inflammatory and fibrotic processes, yet its role in ulcerative colitis (UC) remains unclear. This study aimed to systematically evaluate the expression of GOLM1 in intestinal mucosal tissues and peripheral blood of UC patients, analyze its correlation with clinicopathological features, and investigate its regulatory effect on intestinal mucosal barrier function along with the underlying molecular mechanisms.

Colonic mucosal biopsy specimens and peripheral blood samples were collected from patients with UC (including active and inactive disease) and healthy controls. GOLM1 expression in tissues was assessed via RNA sequencing, immunohistochemistry, western blotting, and quantitative real-time PCR (qPCR), while serum GOLM1 levels were measured by ELISA. Using a dextran sulfate sodium (DSS)-induced mouse colitis model and an LPS-stimulated inflammatory model in NCM460 intestinal epithelial cells, GOLM1 was knocked down in vivo, and both knocked down and overexpressed in vitro, to evaluate its effects on intestinal permeability, tight junction protein expression, and downstream signaling pathways.

GOLM1 expression was elevated in colonic tissues and serum from patients with UC compared with healthy controls. Serum GOLM1 concentrations were associated with clinical disease activity and inflammatory or immune-related markers. Protein interaction assays supported an association between GOLM1 and EGFR. Genetic gain- and loss-of-function experiments implicated EGFR and p38 MAPK signaling in GOLM1-associated alterations in tight junction protein expression and epithelial barrier readouts. In a DSS-induced mouse model of colitis, GOLM1 knockdown alleviated colonic inflammation and improved intestinal barrier function.

GOLM1 interacts with EGFR and promotes intestinal inflammation and epithelial barrier dysfunction in UC through the p38 MAPK signaling pathway. These findings provide new insights into the molecular mechanisms underlying GOLM1-mediated intestinal injury in UC and lay the foundation for further mechanistic investigations.