Targeted Deletion of EPHX2 in Intestinal Epithelial Cells Alleviates DSS-Induced Colitis by Enhancing Goblet Cell Differentiation.

Abstract

Dysregulation of epoxide hydrolase 2 (‌EPHX2) is associated with the pathogenesis of various diseases. However, the functional role of EPHX2 in ulcerative colitis remains unclear. In this study, we demonstrate that EPHX2 plays a critical role in driving the pathological breakdown of barrier integrity in a colitis model. Pharmacological inhibition of EPHX2 significantly ameliorated Dextran Sulfate Sodium (DSS)-induced colitis. Notably, conditional knockout of EPHX2 in intestinal epithelial cells (IECs) conferred protection against colitis-associated mucosal damage. Moreover, EPHX2 deletion in IECs led to increased Muc2 expression and a higher number of goblet cells by promoting goblet cell differentiation, while the expression levels of tight junction proteins (ZO-1, occludin, and claudin-1) remained unchanged. These findings identify a previously unrecognized role of EPHX2 in IECs and suggest that targeting EPHX2 may represent a promising therapeutic strategy for ulcerative colitis.