Abstract:

Objective To investigate whether the pituitary tumor transformation gene 1 （PTTG 1） plays a role in colitis by regulating intestinal epithelial cells pyroptosis. Methods Ten PTTG 1 wild?type （WT） mice and Ten PTTG 1 knockout （KO） mice were randomly divided into 4 groups of 5 each， respectively PTTG1 WT control and experimental group， PTTG1 KO control and experimental group. The mice in the experimental group were given 3% dextran sodium sulfate （DSS） for 6 days to induce acute colitis， and the control group was given sterile double distilled water（ddH₂O）. The disease activity index of the respective group of mice was observed and recorded. Mouse colonic tissue were collected， and the expression levels of NLRP3， ASC， and GSDMD were determined by immunohistochemistry and western blot. In HCoEpiC， PTTG1 expression was knocked down using shRNA， and the cells were subsequently treated with TNF?α to induce inflammation. Then， the expression of GSDMD was detected. Results The expression of PTTG1 was decreased in colonic mucosal tissue in mice with acute colitis（P < 0.01）. Compared with WT mice， the colitis was significantly aggravated in PTTG1 KO mice after 3% DSS treatment. The expression of pyroptosis?related proteins was significantly up?regulated in the colon mucosal tissues of PTTG1 KO experimental mice（P < 0.05）. After knocking down the expression of PTTG1 in HCoEpiC and TNF?α treatment， the expression levels of GSDMD were significantly up?regulated（P < 0.05）. Conclusion PTTG1 reduced pyroptosis in intestinal epithelial cells （IECs）， while PTTG1 loss can enhance IEC pyroptosis， aggravating colonic inflammation.

Key words: ulcerative colitis, PTTG1, pyroptosis, GSDMD