MXRA7: A potential link between macrophage M1 polarization and epithelial Pyroptosis in ulcerative colitis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent colorectal mucosal damage, in which colonic epithelial cell pyroptosis and imbalanced macrophage M1 polarization serve as core pathological features, yet their interaction mechanism remains elusive. Matrix remodeling-associated 7 (MXRA7) has been implicated in inflammatory immune responses and tissue repair, but its role in UC progression is still unclear. In this study, we performed bioinformatics and cell-cell communication analyses using the GSE214695 single-cell RNA sequencing dataset, collected clinical colonic tissues from UC patients, and established a dextran sulfate sodium (DSS)-induced mouse colitis model, complemented by in vitro cell co-culture, gene knockdown/overexpression and molecular biological assays. The results showed that pyroptosis levels, the degree of macrophage M1 polarization, and MXRA7 expression were all significantly upregulated in the colonic tissues of both UC patients and model mice. Mechanistically, macrophage M1 polarization can directly trigger colonic epithelial cell pyroptosis, whereas MXRA7 may, on the one hand, reduce macrophage M1 polarization by inhibiting the NF-κB signaling pathway, and on the other hand, alleviate epithelial cell pyroptosis induced by M1-polarized macrophages. Collectively, MXRA7 may attenuate colonic tissue damage through these dual regulatory mechanisms, thereby serving as a potential regulatory factor or therapeutic target in UC.