Background PGE₂/EP4 signaling pathway can alleviate mucosal damage in ulcerative colitis, but the mechanism of its regulation of endoplasmic reticulum stress is not fully understood.

Objective To clarify the mechanism of PGE₂/EP4 signaling pathway in regulating ER stress in mucosal injury in ulcerative colitis (UC).

Methods Firstly, divide the mice into a model group and a control group, and detect the expression level of EP4 through immunohistochemistry and PCR, by constructing mice UC model, the experimental mice were divided into acute UC group (DSS), PGE₂-treated group (DSS + PGE₂), indomethacin treatment group (DSS + indomethacin), and control group. The disease activity index of mice was observed and recorded. The colonic mucosal tissues were collected to detect the levels of EP4 and GRP78, epithelial cell apoptosis and proliferation after PGE₂ treatment. The expression of β-arrestin1 was downregulated by siRNA in HCT116 cells, then the expression of GRP78 was detected by PGE₂ treatment.

Results EP4 levels decreased and GRP78 levels increased in the colon mucosa of acute UC mice (P<0.05). After PGE₂ treatment, the colon mucosal epithelial cells showed apoptosis, and the UC disease activity index decreased significantly (P<0.05), while EP4 levels and the level of intestinal epithelial cell proliferation increased significantly (P<0.05). The protein level of GRP78 in UC colon mucosa of mice were increased, and it decreased significantly after PGE₂ administration. After knocking down the expression of β-arrestin1by siRNA in HCT116 cells, the expression level of GRP78 was significantly up-regulated (P<0.05).

Conclusion PGE₂/EP4 signaling pathway attenuates mucosal injury by inhibiting endoplasmic reticulum stress signaling in colitis, which inhibits epithelial cell apoptosis and promotes its proliferation.